FDA is moving fast to implement the drug compounding provisions of the new Drug Quality and Security Act (DQSA), issuing new guidance to spur registration by outsourcing facilities just days after President Obama signed the new bill into law. Because FDA cannot compel compounders to opt for agency regulation, implementation will rely largely on market pressures to encourage healthcare providers to purchase compounded products only from registered facilities, explained FDA commissioner Margaret Hamburg at a press briefing Dec. 2, 2013.
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Guest blog written by Walter Morris, Director of Publishing, Parenteral Drug Association, on behalf of the PDA Quality Metrics Task Force
The US FDA Center for Drug Evaluation and Research (CDER) reached out earlier this year to industry and the public for input into plans to implement parts of the 2012 Food Drug Administration Safety and Innovation Act (FDASIA).1 Quality manufacturing leaders in the industry must now seize this opportunity to help bring about real changes to a system of regulatory inspection and enforcement that, in spite of reasonable attempts at reform over the last decade, is struggling with new challenges. Continued high-cost enforcement actions, plant closures, drug shortages and, regrettably, real harm to patients have pushed everyone involved with this industry to recognize, finally, that a new regulatory and quality paradigm is needed.
Public outrage over deaths from contaminated injectibles produced by large compounding pharmacies, along with rising concerns about counterfeit and unauthorized drugs entering the U.S. market, managed to lift the stalemate on Capitol Hill long enough to generate agreement on reform legislation. After months of public hearings and negotiations, Democrat and Republican leaders of the House Energy & Commerce Committee and the Senate Health, Education, Labor and Pensions Committee unveiled a compromise bill last week. No one gets all they wanted from the Drug Quality and Security Act, but it provides more clarity and predictability to drug oversight programs and moves forward initiatives designed to enhance the safety and quality of medicines in the U.S.
Healthcare spending will rise modestly in the US over the next decade, as economic growth picks up, health reform provides expanded coverage, and the population continues to age, according to an annual analysis from the Centers for Medicare and Medicaid Services (CMS). These trends similarly will boost expenditures for prescription drugs, but not as quickly as in previous decades.
Outlays for healthcare in the US have grown much more slowly over the past three years, largely due to an economic decline that deterred individuals from seeing doctors and to increased cost-sharing requirements for the privately insured. Minimal growth is continuing this year, but expenditures will begin to rise in 2014, boosting the average growth rate for national health spending to 5.8% through 2022, according to the National Health Expenditure Projections from the CMS Office of the Actuary and published by Health Affairs. Much of the spending will come from public agencies, as healthcare financed by federal, state, and local governments reaches $2.4 trillion in 2022, nearly half of all national health outlays.
FDA commissioner Margaret Hamburg has formed a top-level working group to propose strategies for enhancing agency functions and processes, starting with the relationship between FDA Centers and its field force. The Program Alignment Group (PAG), announced Sept. 6, 2013, will seek to clarify the roles and responsibilities of product centers and the Office of Regulatory Affairs (ORA) to more effectively align practices, processes, and resources. The panel includes the deputy commissioners for food and veterinary medicine, for global regulatory operations and policy, plus the heads of ORA and all Centers to better coordinate inspection and oversight policies and programs throughout the agency.
Key issues are whether more specialization in FDA inspection and compliance functions would be beneficial, and how risk-based models and performance metrics may improve oversight and compliance outcomes. The agency also is looking for ways to achieve more efficient laboratory operations and to coordinate training for ORA and Center staffs.
Hamburg further explained at a conference on biomedical research the next week that her reorganization effort reflects the impact of a more globalized world for medical product development and production. Historically, ORA has fielded generalists able to inspect and evaluate a broad range of regulated products, but the modern era may require a more specialized regulatory staff. And while these issues have been addressed periodically by FDA Centers, including the Center for Drug Evaluation and Research (CDER), the PAG will seek a more cohesive approach that considers the differences and needs of all regulated product areas.
CDER director Janet Woodcock, who is on the PAG, sees its mission paralleling her initiative to modernize how CDER regulates pharmaceutical quality. Woodcock seeks to establish an Office of Pharmaceutical Quality (OPQ), which similarly would coordinate drug compliance activities with ORA and take steps to clarify roles and responsibilities of CDER offices and to establish metrics and accountability.
At the PDA/FDA joint regulatory conference Sept. 16, Woodcock emphasized that CDER has to change the way it regulates industry to ensure an agile manufacturing sector that can reliably produce quality medicines, with less extensive agency oversight. One innovation would be to reorganize the review of the manufacturing portion of drug applications according to dosage forms and their predictable “failure modes.” Most product recalls, she noted, involve formulation design problems, such as particulates in parenterals and dissolution failures with solid oral products. This approach will involve setting clinically relative specifications and identifying what changes raise risks for drug safety and efficacy – and what do not.
The PAG is slated to give Hamburg an initial plan for operational changes by early December. And CDER hopes that OPQ will become a reality early next year, said Keith Webber, acting director of CDER’s Office of Pharmaceutical Science, at the PDA conference. The reorganization process is slow, as CDER’s OPQ proposal requires approval by HHS officials and has to be vetted by the Office of Management and Budget; some members of Congress also may want to review how the changes could affect drug shortages and patient access to medicines.
Pharmaceutical Research and Manufacturers of America (PhRMA) International Vice-President Jay Taylor has expressed the organization’s concerns over the Office of the United States Trade Representative’s (USTR) 2013 Special 301 Report. The Special 301 Report, released in May 2013, is an annual review of the state of intellectual property (IP) rights protection and enforcement in trading partners around the world and reflects the US Administration’s resolve to maintain IP protection worldwide.
Expressing appreciation for USTR’s efforts to ensure IP protection, Taylor expressed dismay that an out-of-cycle review was not granted for India. “The deteriorating protections for patented medicines in India have become increasingly concerning,” Taylor said in a PhRMA blog. “Over the past year, the Government of India has issued several intellectual property decisions that have disproportionately impacted US biopharmaceutical companies and a number of other innovative sectors. The IP regime in India has been structured and applied in ways that prop up local industries to the detriment of US jobs and the worlds patients.”
Pharmaceutical Technology interviewed some of the speakers for the upcoming INTERPHEX 2013 conference to get a “sneak peek” of their presentations. The first of these, an interview with Par Almhem, president of ModWave and Modular Partners, discusses advances in modularization. Check out the media player on the PharmTech website or click here to listen to the podcast, and look for more to come soon. If you’re at the show, be sure to stop by PharmTech’s booth (Booth #4139).
INTERPHEX 2013 begins later this month and Pharmaceutical Technology will be previewing the action in the weeks to come.
Look for posts from our Manufacturing Editor Jennifer Markarian, as well as PharmTech’s Editorial Director Rita Peters and Executive Editor Patricia Van Arnum.
And be sure to stop by PharmTech’s booth (Booth #4139) during the show!
The US Orphan Drug Act of 1983 defines a rare disease as one that affects fewer than 200,000. There are nearly 7000 rare diseases affecting nearly 30 million—or nearly one in 10—Americans, according to the National Organization for Rare Disorders (NORD).
The National Institutes of Health (NIH) reports that approximately 80% of rare diseases are genetic in origin; about half affect children. The challenges of facing a chronic, disabling, severe, or even life-threatening disease is compounded by difficulties in receiving an accurate diagnosis, and the lack of therapies to address the condition.
For the past six years, the last day in February has been designated Rare Disease Day. First observed in Europe in 2008 by the European Rare Disease Organization, the initiative expanded to the US in 2009. In 2012, more than 60 countries participated.
This year, events will be held worldwide on Feb. 28 to bring the cause of rare diseases to the attention of patients, the public, the medical profession, and policy makers. For example, the NIH is sponsoring a two-day conference for researchers and policymakers, including FDA representatives, to raise awareness of rare diseases, bring stakeholders closer together, coordinate policy actions between nations, and emphasize rare disease research and the search for new therapeutics.
The Orphan Drug Act provides tax credits and marketing incentives for sponsors to develop products for rare diseases. Since 1983, the number of applications submitted and products designated as orphan drugs has continued to grow. More than 400 drugs and biologic products for rare diseases have been approved. In contrast, fewer than 10 such products supported by industry came to market between 1973 and 1983.
Drug makers have financial incentives to develop orphan drugs. A 2012 report from Thomson Reuters, The Economic Power of Orphan Drugs, estimated the orphan-drug market at the end of 2011 at $50 billion globally, or 6% of total pharmaceutical sales. However, a compound annual growth rate (CAGR) of 25.8% for 2001 to 2010, compared to a 20.1% CAGR for a matched group of non-orphan control drugs, and an increasing number of orphan-drug approvals, suggests that the growth rate of orphan drugs will exceed that of non-orphan control drugs over the next 30 years, according to the report. Because many orphan drugs are biologics, they are less susceptible to generic competition than small-molecule drugs.
The impact of the smaller population needing the orphan drug is offset by the high cost of the drugs. In fact, the Thomson Reuters study found that 29% of orphan drugs have annual sales greater than $1 billion, about the same percentage as non-orphan drugs.
While the Orphan Drug Act has spurred the development of life-saving and life-improving therapies for individuals with rare diseases, it also has provided financial incentives for drug companies to invest in these narrow specialties. However, as the sponsors of Rare Disease Day point out, there is still much work to be done.