Daniella (Dee) Latham

Last week the US Food and Drug Administration (FDA) issued a revised draft guidance detailing its policies on mixing, diluting, and repackaging certain types of biological products outside of the scope of an approved biologics license application (BLA).

Diluting or mixing a biological product with other components, or repackaging a biological product by removing it from its approved container-closure system and transferring it to another container-closure system, in the absence of manufacturing controls, is highly likely to affect the safety and/or effectiveness of the biological product. The FDA says even minor manipulations of biologics can result in quality or safety issues due to their unique properties.

There are instances where appropriate to mix or dilute a biological product to meet the needs of specific patients. "For example, for some biological products there is no licensed pediatric strength and/or dosage form, so the product is diluted for use in pediatric patients." While there are exemptions from certain federal regulations for compounded drugs under sections 503A and 503B of the 

, these exemptions do not apply to biological products licensed under sections 351(a) or (k) of the 

In accordance, the FDA says that any biological product that is mixed, diluted, or repackaged outside the scope of an approved BLA is an "unlicensed biological product." It also does not intend to take actions for violations of section 351 of the PHS Act or sections 502(f)(1) or 582 of the FD&C Act if a state-licensed pharmacy, a federal facility, or an outsourcing facility mixes, dilutes, or repackages a biological product" in accordance with the guidance.

The guidance does not apply to investigational new drugs being studied under a new drug application or radioactive biological products.

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Biologics Mixing, Diluting, and Repackaging: FDA Draft Guidance

As more biologics come off patent in the next few years, the opportunities for biosimilars and the impact upon the biotech and pharmaceutical industries are limitless. While it's exciting for physicians, patients, and payers, the US Food and Drug Administration's (FDA) regulatory ruling on biosimilar suffixes has increasingly taken on more urgency. Well, the wait is now over.

The FDA has determined that a suffix will help distinguish biosimilar products and avoid a substitution mistake--and it has has already included four additional letters on the end of each non-proprietory name for existing biosimilars:  Filgrastim, the biologic drug Neupogen, becomes filgrastim-sndz, biosimilar Zarxio. Adalimumab (Humira) becomes adalimumab-atto (Amjevita).

At this point, only four biosimilar drugs are approved in the US, but are not considered interchangeable with their reference biologic. This means pharmacists cannot make a choice whether to give a patient a biosimilar as opposed to a biologic, which is a regular practice with generics and small-molecule drugs.

The new guidance says each suffix can not have a specific meaning attached to it and must include four lowercase letters.

The suspense is over: the US Food and Drug Administration (FDA) has made their decision.

Bio Relief: US FDA Rules On Biosimilars Naming 

The long awaited news conference from then President-Elect Trump in early January didn't disappoint in terms of drama, nor bode well for the country's most well-known and financially-lucrative pharmaceutical companies.

Only Merck remained unscathed among the top-tier drug manufacturers in the Dow--stock was up 2.6%. Merck was the Dow's best performer in the sector, due to the US Food and Drug Administration's (FDA) acceptance of a bid for an accelerated review of an immune-system drug to be used with chemotherapy for advanced lung cancer patients.

, Mr. Trump inferred that many drugs are manufactured outside the US, and that , "A lot of industries are going to be coming back. We have to get our drug industry coming back. Our drug industry has been disastrous. They’re leaving left and right. They supply our drugs, but they don't make them here. To a large extent. And the other thing we have to do is create a new bidding procedures for the drug industry because they're getting away with murder."

"Pharma has a lot of lobbies, a lot of lobbyists and a lot of power. And there's very little bidding on drugs. We’re the largest buyer of drugs in the world, and yet we don't bid properly. And were going to start bidding and were going to save billions of dollars over a period of time", stated Trump. 

Does this mean Medicare will negotiate drug prices in the future? 

With more people entering the Medicare system over the next eight years, this will be more than just a radical shift in a federal program that is already financially burdened beyond its capacity. Medicare is the largest buyer of drugs in the US, and that means all private insurance companies that participate in the Medicare marketplace will be able to negotiate prices with the drug companies. Estimates are the 

federal government could save as much as $16 billion

 annually by negotiating prices directly--which is way below the $300 billion figure 

mentioned by Trump when he was a candidate.

pharmaceutical stakeholders will be impacted

 -- but can Medicare give a price ultimatum that drug companies must take? We don't know yet. Trump has said that pharmaceutical organizations have a responsibility to the public, even though they are privately-owned entities. The end result will hopefully be a compromise.

Patients may save money on prescriptions---and cut down pharma's profits.

What President Trump Means for Big Pharma

Mylan said today it will partner with Momenta Pharmaceuticals to develop, manufacture, and commercialize six of Momenta’s current biosimilar candidates, including Orencia® (abatacept), in a collaboration that could generate up to $245 million for Momenta, as reported by GEN magazine.

The collaboration is designed to combine Momenta’s biosimilars with Mylan's global R&D, supply chain, and commercial infrastructure. Mylan said the companies will be jointly responsible for product development, with Mylan leading worldwide commercialization efforts.

In a separate statement, Momenta said it will have an option to co-commercialize in a supporting commercial role any approved products in the U.S.

In return, Mylan agreed to pay Momenta $45 million in up-front cash, plus up to $200 million in payments tied to achieving milestones. The companies will share equally in the costs and profits of the biosimilars with respect to the products.

Momenta’s biosimilar pipeline, according to the company’s website, includes nine programs, only two of them disclosed—Orencia (M834) and the company’s lead biosimilar candidate M923, a biosimilar version of Humira® (adalimumab).

Last month, Momenta said M923 met its primary endpoint in a pharmacokinetic study comparing the biosimilar to U.S. and EU Humira reference products in patients with chronic plaque psoriasis. Momenta said it is planning its first regulatory submission for M923 in 2017, and its first commercial launch the following year.

Orencia and the seven unnamed biosimilars are in preclinical phases, with Orencia expected to advance into the clinic this year for moderate to severe rheumatoid arthritis in adults and juvenile rheumatoid arthritis.

Mylan said the partnership with Momenta will complement a biosimilars and insulin analog alliance with Biocon 

, and will position Mylan as “a definitive world leader” in biosimilars with a portfolio to 15 biosimilar or insulin analog generic products in development.

“This collaboration builds upon Mylan's existing successful biologics and insulins collaboration with Biocon, which is focused on more near-term biosimilar opportunities,” Mylan CEO Heather Bresch said in a statement.

The Biocon partnership includes programs to develop biosimilars for six compounds—trastuzumab, pegfilgrastim, adalimumab, bevacizumab, etanercept, and filgrastim&mdash;as well as three insulin analogs&mdash;glargine, lispro, and aspart. Mylan said five of those biosimilar programs have successfully completed Phase I clinical trials, while four are in Phase III studies.

Mylan and Biocon expect to submit three biosimilar applications and one insulin application in the U.S. and Europe this year. Mylan already has successfully launched its trastuzumab biosimilar product in India and other emerging markets.

Mylan and Momenta Pharmaceuticals to develop, manufacture, and commercialize six of Momenta’s current biosimilar candidates.

Mylan and Momenta Pharma Combine Biosimilar Forces

On December 29, the US Food and Drug Administration (FDA) finalized long-awaited biosimilar guidance from 2014 on the needed clinical pharmacology data from pharmaceutical sponsors.

“Clinical pharmacology studies are part of a stepwise approach for developing the data and information needed to support a demonstration of biosimilarity,” said the FDA. “These studies can reduce the residual uncertainty in assessing the biosimilarity between a proposed biosimilar product and reference product and inform the design of subsequent clinical trials to assess clinically meaningful differences.”

Biologics Price Competition and Innovation Act of 2009

 (BPCIA) created the original approval pathway for follow-on biologics, and guidance on interchangeability is expected this year, containing recommendations on how clinical pharmacology studies that assess the presence or absence of clinically meaningful differences between the proposed biosimilar and the reference product should be conducted and analyzed.

There are four areas upon which the new guidance focuses:

The role of clinical pharmacology studies in the demonstration of biosimilarity

Critical considerations in the use of clinical pharmacology studies to support biosimilarity (with subsections on safety and immunogenicity, among others)

Developing clinical pharmacology data for supporting a demonstration of biosimilarity (with subsections on study design, pharmacokinetic (PK)

Pharmacodynamic (PD) measures, among others) and the utility of simulation tools in study design and data analysis

It has been a long 20 months for drug manufacturers who have been awaiting the update to the original draft version, and had taken issue with the FDA's four possible outcomes and terminology for the analytical comparison of the reference product and proposed biosimilar drug.

FDA Finalizes Biosimilar Guidance

According to Reuters, The US Supreme Court has declined to hear a case over whether companies that make copycat versions of biologic drugs must wait six months after winning federal approval before bringing them to the market.

The justices opted not to take up Apotex Inc's appeal of a July federal appeals court ruling that could delay the Canadian generic drug maker's launch of so-called biosimilar versions of California-based Amgen Inc's Neulasta, used to fight infection in cancer patients.

The biosimilars law gives the maker of a biologic drug 12 years of exclusive rights before the US Food and Drug Administration can approve a biosimilar. It also states that a biosimilar maker must give the original biologic drug maker 180 days' notice before launching its copycat version.