The next boom in Pharma market – BIOLOGICS & BIOSIMILARS

Yes, you read it right! Though this topic is highly prevalent in the Pharma industry, it would be surprising to know, how this subject influences a high profit turnover. Keep reading and find some interesting facts.

CHEMICAL DRUGS vs BIOLOGICS: It is important to understand the difference between Chemical drugs (also known as pharmaceuticals) and Biologics (also known as biological medicines). A pharmaceutical has a base of chemical substances or small molecules, whereas, a biologic or biopharmaceutical is a protein based molecule or large molecule, which is processed by Recombinant DNA (rDNA) technology. To gain more insights on these chemical drugs/ pharmaceuticals and biologics/ biological medicines, let’s review them separately. The highlights of these drugs are individually described below:

BRANDED DRUGS and GENERICS: Pharmaceuticals consist of branded drugs and generics. As described above, Pharmaceuticals are small molecules, simple in structure that are well understood as well as studied. The stability of the active ingredients in these drugs, could be enhanced as degradation of compounds is a highly known phenomena. A chemical drug comes with the biggest ease for the manufacturers as they can be completely characterized for various properties. Hence, various organic and inorganic chemical principles can be applied to obtain the finished formulations in different dose forms. Such properties though sound easy but they do have efforts and investment involved, however, are advantageous over the biologics. Yet, as every coin has two sides, our very own Chemical drugs too, have a major drawback in terms of potency i.e., they have potentially low therapeutic value in comparison to the Biologics. The branded drugs, also called “innovator drugs” are those that are initially marketed as “new chemical entities” with a unique proprietary name or “brand name” by its proprietor or innovator. Generics, that are known as “copy drugs” of the innovator or brand drugs are great alternatives. These are low in cost, hence are easily available in market but are as effective as their brand counterparts. Effective? How? Generics, the copy drugs are identical to their Brand drugs. They are and should be identical to the reference products in terms of dosage form, safety, strength, route of administration, quality in terms of purity, efficacy and intended use. Brand drugs have patent liberty and protection in the market for 20 years, which doesn’t allow anyone else to manufacture and market their drugs.

Other Pharma companies on other hand, may enter during the expiry of the innovator drug patents with the generic version of such drugs. According to the FDA, such generic companies need to submit an “abbreviated new drug application” (ANDA) unlike innovator drug applications known as “new drug application” (NDA) for approval to market a generic product, under the Drug Price Competition and Patent Term Restoration Act of 1984, more commonly known as the Hatch-Waxman Act. The Brand name drugs and the generics are listed well under the US FDA’s “Orange Book”. There are no complex requirements that the generic drug manufacturers need to establish against the reference drug, except the bioequivalence tests, whose results are required to be identical to their reference drugs along with other parameters.

BIOLOGICS and BIOSIMILARS: A medicine derived out of variety of living sources such as human, plant, animal, or microorganisms is known as a Biologic or Biological medicines. As described earlier these are nothing but proteins derived out of the diverse sources. These are specifically targeted for the treatment of human diseases. Examples of Biologic medicines are hormones, enzymes, antibodies, specifically monoclonal antibodies, vaccines, blood factors, etc. The copies of Biologics are known as “Biosimilars”. A biosimilar is not like a generic as the generic needs only bioequivalence tests to prove its equivalence to its standard but a biosimilar drug needs to surpass various troughs and crests against its biologic as these are highly sensitive, complex large molecules. Hence, as Biologic cannot be a chemical drug the same way a Biosimilar cannot be a mere Generic.

But yes, it is a noteworthy fact that Biological medicines; as are proteinaceous in nature, are highly specific to their target. These targets also being proteinaceous in nature, the resultant protein to protein interaction is highly specific and the biologic has high therapeutic value on the particular disease than the pharmaceuticals. In addition, as there is increase in size, there is increase in complexity and stability, Biological medicines are generally manufactured to be Lyophilized powders administered through various parenteral routes.


BIOSIMILAR Approval Pathway: As Theodore Roosevelt rightly said, “Nothing in the world is worth having or worth doing unless it means effort, pain, difficulty…”, so is the approval of Biosimilars. A small-molecule generic drug is a simplified manufacturing methodology as only simple active ingredients are involved. On the other hand, Biosimilars are highly challenging for its manufacturers as these proteins are highly sensitive to their environment and any mild deviation in the planned procedure may lead to degradation or undesired changes in the proteins. Hence, the Biosimilar players need to be very cautious in picking up a unique protocol and conducive environment to create same therapeutic outcome as to the standard Biologic, i.e. the Biologic and the Biosimilar should be clinically meaningful and indifferent.

As per the FDA, the Biologics License Application (BLA) is the application to introduce, manufacture or sell a biological medicine under the pathway authorized by the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). The BPCI Act is similar in concept to the Drug Price Competition and Patent Term Restoration Act of 1984 (the "Hatch-Waxman Act"), which enables approval of generic drugs based on their comparison to already approved drugs. The BPCI Act amends the Public Health Service Act (PHS Act) and other statutes to create an abbreviated licensure pathway in section 351(k) of the PHS Act for biological products shown to be biosimilar to, or interchangeable with, an FDA-licensed biological reference product. Interchangeability is the medical practice of changing one medicine for another. The change is such that same clinical effect in a given clinical setting is present on any patient, or with the agreement of the prescriber.

The Biologics and the Biosimilars are listed well under the US FDA’s “Purple Book”. The Biologic enjoys a protection of 12-year exclusivity from the date of first licensure of the reference product, after the expiry of which a Biosimilar may enter the market. An abbreviated Biologics License Application (aBLA) can be submitted however after 4 years from the date of first licensure of the reference product (Biologic), however marketing grant of aBLA will be after the 12-year expiry period of the same.                                                                                   

The PHARMA Boom Factor!!!

According to a report by Mari Serebrov, Regulatory Editor, BioWorld, The FDA in the year 2015, has approved over 12 new BLAs and around 45 total number of NME (New Molecular Entity) / BLA has been approved with 26.5% of new approvals.  The European Pharma market have the most advanced Biosimilar market globally with 7 classes, 12 molecules and 20 brands so far. The major Biosimilar players are Sandoz (Germany), Hospira (USA) and Teva (Israel) globally; Dr. Reddy’s Laboratories, Biocon Limited and Intas Biopharmaceutical Ltd. in India.

It is interesting to know that the new way to tackle the Biomarket Competition is “collaborations”. The strategic alliances from 2010 to 2013 was witnessed between Biocon and Mylan, Amgen with Merck and Celltrion (Japan) with Hospira. Apart from that Pfizer in September 2015, bought Hospira, a much smaller company in its comparison, so that the acquaintance may lead to its entry into the Biosimilar world along with sterile injectable portfolio at the expense of $17 billion. Many Asian countries such as China, India and South Korea along with Australia, Brazil are expected to witness growth in double digits by 2018.

 It would be interesting to see how with the lengthy Clinical trials processes required to establish that the Biosimilar is identical to its Biologic, the key players would take part in this race for Biosimilars. According to IMS, “Biologic agents will continue to outpace overall pharma spending growth and are expected to represent 19-20% of the total market value by 2017 with the industry growing up to $221 Billion globally”. The good news for the industry is, with many of the Biologic companies who have market share worth $81 billion and above, have their patents expiring by 2020, the race for Biosimilars has been intensified and many top Pharma companies including Mylan, AbbVie, Roche, Pfizer, etc. have their sleeves rolled up.

 Hence, Biosimilars would turn out to be like “the cherry on top of the cake” for the public as the Biosimilars have targeted treatments not only for diseases such as Cancers, autoimmune diseases, Rheumatoid arthritis, Crohn’s disease, etc., also they will be available in the market for an affordable price than the Standard Biologic. Hence, both the Biosimilar players and the public would be benefitted. As Biosimilars as well as Generics are mostly given authorizations by the government in interest of the public, hope these medicines reach people without any deficiency in its supply. The Indian Pharma industries should surely gear up to have collaborated manufacturing and marketing plants, so as to gain momentum over the Biosimilar market and to curb on the expenses to develop such drugs.  

By: Kavitha Naidu, Trainee-Clinical Research at Zenvision Pharma and can be reached at