US Pharm. 2013;38(6)(Generic Drug Review suppl):18-23.

The Generic Pharmaceutical Association (GPhA) is a trade association founded in 2000 for manufacturers and distributors of generic prescription drugs, manufacturers of bulk active pharmaceutical chemicals, and suppliers of other goods and services to the generic industry. According to Claire Sheahan, vice president for communications for the GPhA, “We are a unified voice representing the industry before federal and state law-makers, regulatory policymakers, and international agencies advancing the interests of member companies. The mission of the GPhA is to improve the lives of consumers by providing timely access to affordable pharmaceuticals. The member companies of the GPhA manufacture the majority of all pharmaceuticals dispensed in the United States with products that are used in nearly 4 billion prescriptions every year,” noted Ms. Sheahan.



Ralph G. Neas was selected as the association’s new president and chief executive officer in September 2011. Mr. Neas joined the GPhA team after serving as president and CEO of the National Coalition on Health Care (NCHC), where he championed efforts to control costs and improve care in the U.S. health care system.

Biosimilar Medicine

Biologic therapies include an array of products used to treat certain health conditions. Human and/or animal materials are used as a basis for these product formulations and include vaccines, blood components, genetic therapy, and tissue proteins. According to the FDA, a biosimilar is a “biological product that is similar to an approved biological product, that may include minor differences in clinically inactive components, and for which there are no clinically meaningful differences in the safety and potency between the biosimilar and the approved biological product.”

The Affordable Care Act (ACA) authorized the FDA to develop regulations for the approval of less-costly biosimilar medicines. While biosimilar products are available in other highly regulated markets, including but not limited to Canada and Japan, the FDA is now responsible for developing guidance and regulations for these agents in the United States.

Q: What is the status of FDA rule making on the regulatory pathway for brand to generic on biosimilar agents?
A: The FDA is still in the development stages of draft guidance. It put out the first draft in January of 2012 and we, along with scores of other interested parties, responded in April and May of 2012. We are now waiting for the next draft. To date, there is not a defined pathway.

Q: What are the outcomes and ramifications for patients?
A: The impact on patients is direct and meaningful: more choices and more access. For example, the cost of treatment for a patient on Avastin, a biologic therapy for cancer, is currently nearly $100,000. With the advent of biosimilars, economic estimates of savings are between 20% and 50%. For Avastin, that’s a savings of $20,000 to $50,000 per year. As we have seen with generic drugs in the small-molecule world, price and access are directly related. As prices go down, access goes up, and more people can reap the benefits of these breakthrough medicines.

Q: What is the future of biosimilars and where are you in this process?
A: The future is bright for biosimilars and the companies making them. In Europe, biosimilars have been in the marketplace since 2006, and taken together, eight countries with biosimilars now say that they expect to save $40 billion by 2020. Several of our member companies have biosimilars in their pipeline. Once the FDA guidelines come forth, you will see applications filed, and the U.S. can start catching up with other parts of the world where they are benefiting from these newer versions of life-saving biologic medicines, with no atypical safety issues. Our companies are eagerly waiting for the FDA to make public their draft guidance, so that we can take the next steps to deliver on the promise of these lower cost, high-quality new versions of biologic medicines for patients, payers, and the health system as a whole.

Q: Has the ACA created any impact on the generic industry overall and specifically on the issue of biologic products that have lost their patent protection?
A: The ACA will have major effects on the health care industry. With more than 30 million more Americans newly able to purchase health insurance, there will likely be an increase in the use of health services, and even greater need to control health costs. Many criticized the ACA because while it expanded access to health coverage dramatically, there was not as much focus on cost savings. In fact, we believe that a more reasonable timeline for “market exclusivity” for biologic medicine could help save millions more. However, including the biosimilars pathway language in the ACA was an important cost-saving measure since it provided for the FDA to create a pathway for cost-saving biosimilar medicines.

Q: Since regulation for generic interchange varies by state, what, if any, effort by the states is being considered before the FDA is done?
A: Regulation of biosimilar interchangeability is the responsibility of the FDA. States will likely need to amend their current legislation, once the FDA has issued guidance, to account for new biosimilar dispensation. However, current efforts in the states by Amgen and Genentech are being proposed as “safety” measures and are little more than burdensome red-tape provisions designed to create barriers to prescribing new lower cost medicines. In some states, like Mississippi, state legislators have declined to act on this legislation while there are still so many unknowns from the FDA. Bills are currently under consideration in 13 states: Arizona, Arkansas, Colorado, Florida, Indiana, Maryland, Massachusetts, North Dakota, Oregon, Pennsylvania, Texas, Virginia, and Washington.

Drugs of Diversion and Deterrent Formulations

According to the FDA, modern prescription pain management must include the appropriate use of opioid analgesics. The abuse of these products, however, has created a serious growing danger to public health. The FDA has worked to address this problem with the development and use of opioids that are formulated to deter abuse. Opioid analgesics can be abused in a number of ways, including swallowing whole or crushed pills, crushing and then snorting, smoking or dissolving, and injecting; thus, the deterrent strategies target these abuse pathways.

The FDA categorizes abuse-deterrent formulations in the following way (accessed from the FDA Web site on February 25, 2013):
Physical/Chemical Barriers—Prevent chewing, crushing, cutting, grating, or grinding. Chemical barriers can resist extraction of the opioid using common solvents like water, alcohol, or other organic compounds. Physical and chemical barriers can change the physical form of an oral drug, rendering it less amenable to abuse.
Agonist/Antagonist Combinations—An opioid antagonist can be added to interfere with, reduce, or defeat the euphoria associated with abuse. The antagonist can be sequestered and released only upon manipulation of the product.
Aversion—Substances can be combined to produce an unpleasant effect if the dosage form is manipulated prior to ingestion or a higher dosage than directed is used.
Delivery System (including depot injectable formulations and implants)—Certain drug-release designs or the method of drug delivery can offer resistance to abuse. For example, a sustained-release depot injectable formulation that is administered intramuscularly or a subcutaneous implant can be more difficult to manipulate.
Prodrug—A prodrug that lacks opioid activity until transformed in the gastrointestinal tract can be unattractive for intravenous injection or intranasal routes of abuse.

The FDA considers the development of these abuse-deterrent formulation products a public health priority; however, the GPhA has concerns about making these formulations affordable by allowing generic interchange of these products.

Q: In light of the recent press regarding the heightened scrutiny on drugs that are high risk for diversion and abuse, what is the status of generic Opana (oxymorphone) and Oxycontin (oxycodone)?
A: Opana’s patents have now expired and generic competition has entered the market. Oxycontin is still under patent so there is no generic competition at this time.

Q: Does the FDA have any draft guidance on these abuse-resistant formulations?
A: Yes, it was placed into the Federal Register on January 9, 2013.

Q: There has been some discussion about recent patent expirations, prompting lobbying efforts by manufacturers to gain political support to prevent generic approvals based on the “lack of equally robust tamper resistant” technology.  What is the status of the efforts to limit the generic versions of these opioid products?
A: None that we are aware of at this time. The FDA is better positioned to answer this question.

Q: How important is the role of education in the proper use of these products, versus the abuse-deterrent features?
A: If there were one simple answer to preventing the tragedy of drug abuse, certainly we would have ended it by now. Abuse-deterrent formulations should be only one tool in the toolbox; education of physicians and patients are important as well. Many states operate prescription drug monitoring programs that effectively monitor drugs within that state, but more can be done. Education is an extremely important tool in the fight on opioid abuse.

March 25, 2013 Supreme Court Hearing on Patent Settlements

The Hatch-Waxman Act allows a generic drug company to file an application with the [FDA] to create a generic version of the original product. In theory, the filing of a generic application can be considered an infringement of patent and opens the doors for patent lawsuits. Most of these suits are settled with an agreement between parties that prevents the production of a generic version of the drug for a specific time period in exchange for a payment from the original manufacturer to the generic manufacturer. These agreements have become known as  “pay-for-delay” agreements. The Federal Trade Commission (FTC) recently filed a brief with the U.S. Supreme Court in order to explore the legality of these arguments in light of antitrust laws. The FTC filed the preliminary brief on January 22, 2013, and a hearing for oral argument was held on March 25, 2013.

Q: What do you see as a potential outcome from the March 25th U.S. Supreme Court hearing for oral arguments pertaining to the issue of patent settlements?
A: We believe that the Supreme Court will agree with the majority of appellate court decisions, which have upheld the validity of patent settlements. The recent 3rd district decision was an outlier.

Q: What are the current circumstances surrounding a successful patent overturn (i.e., of a frivolous patent)?
A: It is important that we do not confuse a patent settlement with the invalidation of a patent. A settlement does not invalidate a patent. However, the GPhA has long maintained that patent settlements are a vital tool for providing patients with early access to safe and affordable generic medications. Over the past 10 years, patent settlements have enabled dozens of first-time generics to come to market many months and even years before patents on the counterpart brand drugs expired. In fact, 17 of the 22 first-time generics launched in 2011 were the result of patent settlements, including Zyprexa, Solodyne, Levaquin, and Lipitor. Ultimately, these patent settlements have saved consumers and the health care system billions of dollars.

Q: Hatch-Waxman was intended to incentivize and foster competition. What do you see happening to the generic company’s initiative to get new generics to market should this settlement prohibition pass?
A: If a prohibition on proconsumer, procompetitive patent settlement passes, it will have a chilling effect on the number of paragraph IV challenges our member companies bring and, as a result, will lower the number of generic drugs on the market before the patent expires. Filing a paragraph IV challenge is an expensive and risky proposition. The patent is either valid or invalid. There is no middle ground. Taking away the constitutional right of two private parties to settle their litigation would only increase the level of risk for a brand and generic company. As the level of risk increases, the less likely a generic company will bring a patent challenge and, consequently, the fewer generic drugs will reach the market prior to patent expiration. This is especially true for smaller generic drug companies that may only bring one or two patent challenges in their lifetime.

Q: Is this the same thing as pay-for-delay that is going to the Supreme Court? If not—how is it different?  Tell us more about this fight.
A: The Supreme Court is considering whether settlements are lawful or violate federal antitrust laws. Patent settlements are procompetitive and proconsumer. Settlements consistently bring generic products to the market months, if not years, before the patent expires.

Q: Can you remind us of the current time line for generic drug approvals and patent trademark durations? Do you see these ever changing?
A: Currently, the median review and approval time for a generic drug application is over 30 months. However, we believe the Generic Drug User Fee Act (GDUFA) that industry negotiated with the FDA will significantly reduce the review and approval time to around 15 months over the next few years. We believe that the GDUFA process will have a profoundly positive effect on the generic drug approval process. The patent term for pharmaceutical products is 20 years. We do not anticipate that changing.

Generic Drug Shortages

The FDA has acknowledged that the increasing number of drug shortages has become a health care crisis, and officials have been working closely with industry, health care providers, and patients to prevent and reduce the impact of shortages of drugs used to treat or prevent a serious disease or medical condition for which there is no alternative medicine available in adequate supply.
According to the FDA, the number of drug shortages has tripled over the last 6 years—from 61 drug products in 2005 to 178 in 2010—and has disproportionately affected the generic sterile injectable supply market.

Q: What is the position of the GPhA on the current generic drug shortages and the ability of companies to discontinue product lines for life-saving medications? Do you have any suggestions for the FDA or government to support these critical medications if they are discontinued for lack of profit?
A: To solve the problem, it’s critical to understand how shortages happen, and to recognize there is not a single contributing factor. Instead, there are multiple variables, including everything from an insufficient supply of available raw materials, to increasing consumer demand, to decreasing available capacity due to quality and/or compliance issues as a result of FDA activities, to inadequate and delayed communications about shortages. The GPhA believes it is critical that generic manufacturers, and all stakeholders, continue to work together in an effort to solve the problem.

We have worked with the FDA and other stakeholders to provide a multiprong offensive to address current drug shortages and avert future shortages. This includes our support of the enactment of GDUFA and the Accelerated Recovery Initiative, which is an unprecedented multistakeholder proposal to address drug shortages.

Q: Can you comment on the definition of an “authorized generic” and what the practicing pharmacist should know about these generics?
A: Authorized generics compete with generic products in that they are identical to their brand counterpart in both active and inactive ingredients, whereas, according to the FDA’s Office of Generic Drugs, generic drugs are required to contain only the identical active ingredients as the brand.

The Future

Q: What is ahead in 2013 for the industry?
A: In 2013, we expect to do two things: grow and evolve. According to the IMS Institute for Healthcare Informatics, a leading provider of information services and technology for the health care industry, generics today save the U.S. [money] at a rate of $1 billion every other day. That means $1 trillion over the past decade and $193 billion in 2011 alone. But for our companies, that is not enough. They strive every day to meet the needs of tomorrow’s marketplace and tomorrow’s patients. To keep up with increased competition, emerging markets, and trends like specialized patient needs, our companies will continue to adapt and grow. They will build, consolidate, and enhance their technology to achieve economies of scale and to meet growing worldwide demand.

Q: You mentioned that generic medications are the only certain medical intervention that saves real money. Can you expand that in terms of statistics and dollars saved?
A: At a time when nearly every other part of health care is growing more costly, the generic industry continues to innovate to provide high-quality medicines at a fraction of the price of the innovators. Our companies make what people around the globe need—top-quality medicine at an affordable price. In Europe, for example, eight countries will likely save more than $40 billion by 2020 by using biosimilar medicines. As European economies struggle, you can see why products that save tens of billions of dollars are not just changing lives; they are contributing to sustainable health care solutions.

This interview was conducted for U.S. Pharmacist by Tammie Lee Demler, BS, PharmD, BCPP,
Director of Pharmacy Services, Buffalo Psychiatric Center, Buffalo, New York, and Clinical Assistant Professor and Director Pharmacy Practice/Psychiatry Residency Program, University of Buffalo School of Pharmacy and Pharmaceutical Sciences.



To comment on this article, contact rdavidson@uspharmcist.com.