Archive for the 'Regulation' Category

Health Reform May Boost Illicit Drug Sales

Health plans that limit drug converge may encourage consumers to obtain medicines illegally, according to pharmacy experts. Marv Shepherd, director of the Center for Pharmacoeconomic Studies at the University of Texas College of Pharmacy and others noted at the Partnership for Safe Medicines Interchange in October in Washington that an increase in narrow health plan formularies that carry only one or two drugs per class or category will boost purchases of substandard, counterfeit and diverted prescription medicines through illicit operators. Patients accustomed to treatment with a certain drug may seek out other sources of supply if a streamlined plan fails to provide coverage for that medicine, explained Bryan Liang, anesthesiologist and law professor at the University of California San Diego.

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Woodcock Committed to New Drug Quality Office

Establishing a new Office of Product Quality in the Center for Drug Evaluation and Research (CDER) is a top priority for CDER director Janet Woodcock, and she plans to take charge of the operation personally when it is established next year. Her much-discussed reorganization effort is not just an exercise in moving around boxes, but aims to ensure the delivery of quality medications to patients, she explained at the Generic Pharmaceutical Association’s Fall Technical Conference in October.

Woodcock expects OPQ to become operational in 2014, and is moving forward with completion of a concept of operations for the new office, along with an organizational structure. But it is “not a done deal,” Woodcock observed at the ISPE annual meeting last month. She expects it will take at least six months for the new organization “to become real.”

One aim is to establish “one voice for how FDA regulations drug quality”––within CDER and in its relationships with other FDA of offices and other regulatory authorities. This will apply to new drugs, generics, over-the-counter products––biotech therapies and small molecules alike.

OPQ will form specialized staffs for product review and for inspections, with specific units to handle active pharmaceutical ingredients, new drugs, biotech products, and “life cycle drugs” (i.e., generics). OPQ also will bring together microbiologists for all products to provide a unified approach to microbiology.

A new Office of Surveillance in OPQ will oversee quality performance at facilities through pre-approval and routine inspections, with an eye to evaluating if an operation meets performance metrics that indicate a quality operation. And a Policy Office will issue guidance and regulations, while ensuring consistency in CDER actions. Surveillance will be enhanced by CDER gaining more complete information on its inventory of establishments, an undertaking that ideally will lead to less frequent field inspections.

Another theme is to “mitigate risks” by applying appropriate measures and analytical methods to different products. Woodcock expects risk assessment for every product to evaluate critical issues and employ statistically valid sampling.

The main aim of this reorganization is to achieve a “culture of quality in industry,” Woodcock said at the ISPE meeting. These plans will require considerable change within FDA and in industry, and manufacturers, she added, have to recognize that there is a “cost to poor quality.”

Regulatory and QA/QC Focus: Elemental Impurity Analysis

Patricia Van Arnum PharmTech editorAs the pharmaceutical industry prepares for changes to compendial and regulatory standards for elemental impurity analysis, QA/QC and laboratory scientists are tasked with adapting their operations to include data management, analysis, and reporting based on inductively coupled plasma–mass spectrometry (ICP–MS). Understanding the necessary technical controls to implement and manage analytical operations is crucial to ensure regulatory compliance. Pharmaceutical Technology will present a live educational webcast, “Achieving Regulatory Compliance When Moving to ICP-MS for Elemental Impurity Analysis,” on Wednesday, November 6, 11:00 AM to 12:00 PM EST to provide insight from leading industry experts on ICH, USP, and EMA guidelines for elemental impurity analysis and best practices and strategies to optimize the analytical workflow, data management, and data reporting when using ICP-MS. Read more »

Preparing for Regulatory Inspections

Patricia Van Arnum PharmTech editorRegulatory compliance is of paramount importance to pharmaceutical and biopharmaceutical companies, which must be continually prepared for inspections by FDA, EMA, and other health authorities to meet requirements for good clinical practices (GCP) and good manufacturing practices (GMP). Pharmaceutical Technology will present an educational webcast on Thursday Nov. 7th from 1:00 to 2:00 PM EST, “Ensuring Preparedness for Regulatory Inspections,” which will provide insight on inspection trends and practical advice on how to best prepare for GCP/GMP inspections, examine the key information/documentation sought by regulators, and ways to achieve operational efficiency for providing access to that information. Read more »

Industry Needs to Drive the Dialogue Regarding FDA’s Quality Metrics Initiative

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.

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Shutdown Forces FDA, HHS No-Shows

Officials from FDA and the National Institutes of Health (NIH) were scheduled to explain developments in clinical trial registration and transparency at the Drug Information Association’s conference on Clinical Trial Disclosure in Bethesda, Md. this week. They sent in slides, and one HHS official even pre-recorded his presentation. But the government shutdown kept them from showing up in person.

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Budget Showdown Leads to Partial FDA Shutdown

US government agencies, including FDA, faced the first shutdown in 17 years when the House of Representatives and Senate failed to reach agreement on a budget. While national parks and landmarks, including the Statue of Liberty were closed on October 1 and thousands of government workers were idled, FDA expects to retain approximately 55% of its staff during the current partial government shutdown.

According to a Department of Health and Human Services statement, FDA will continue limited activities related to its user fee-funded programs. The agency will also continue “select vital activities including maintaining critical consumer protection to handle emergencies, high-risk recalls, civil and criminal investigations, import entry review, and other critical public health issues.”

The agency reports that it will not support the majority of its food safety, nutrition, and cosmetics activities and may have to cease safety activities such as “routine establishment inspections, some compliance and enforcement activities, monitoring of imports, notification programs (e.g., food contact substances, infant formula), and the majority of the laboratory research necessary to inform public health decision-making.

Reviews of pending approvals for several drugs, originally scheduled for early October, were uncertain as of Oct. 1.

A provision by House Republicans to delay the implementation of the Affordable Care Act appears to be the major sticking point to an agreement. If elected officials get past this roadblock, the next big debate, over increasing the debt ceiling, is just two weeks away.

FDA, CDER Weigh Organizational Changes

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.

Meeting Technical and Regulatory Requirements for Organic Impurity Control and Analysis

Patricia Van Arnum PharmTech editorProduct quality is of paramount importance to pharmaceutical manufacturers, and implementing a strategy for impurity control is crucial. Organic impurities cover a wide spectrum of compounds that have varying structures, behaviors, and characteristics. Organic impurities can result from the manufacturing process, storage conditions, or degradation resulting from light, heat, and other external factors. Deciding what technology or analytical methods to use to detect and measure organic impurities is a challenge. Pharmaceutical Technology will hold a live educational webcast, “Meeting Regulatory and Technical Requirements for Organic Impurity Analysis, on Tuesday Sept. 24 at 11:00 AM EDT to 12:00 PM EDT to provide insight on the regulatory, compendial, and ICH requirements for organic impurity control and analysis as well as best practices in analytical method development, method selection, and method validation for detecting and quantifying organic impurities in drug substances and drug products.

The panelists for the webcast will be: Timothy Watson, PhD, and research fellow in the GCMC Advisory Office at Pfizer and a member of the PhRMA Expert Working Group on the ICH Q11 regulatory guidance document for drug substances; Mark Argentine, PhD, senior research advisor, analytical sciences R&D with Eli Lilly; and Hildegard Bruemmer, PhD, operational laboratory manager, SGS Life Science Services, Berlin. The panelists will provide insight on the regulatory and compendial requirements for organic impurity control and analysis in drug substances and drug products. They will also share insight on selecting the appropriate analytical methods for the detection, analysis, and quantification of organic impurities and offer related case studies on how best to ensure product quality.

Audience members may ask questions of the panelists during the live webcast. Information on how to register for the webcast, “Meeting Regulatory and Technical Requirements for Organic Impurity Analysis” for Tuesday Sept. 24 at 11:00 AM EDT to 12:00 PM EDT and for on-demand viewing is available here.

True Pharma Innovation Lies in Quality, not Quantity, of Approvals, say FDA Analysts

We’re already embroiled in the annual speculation game about whether FDA approvals this year will keep pace with last year’s near-record of 39 new molecular entities (NMEs) brought to market. The tally is closely watched as a sign of the state of biopharmaceutical innovation and the health of the pharmaceutical industry and biomedical research enterprise.

But this focus on the quantity of new drug approvals is misleading, according to FDA analysts, because it fails to distinguish between truly innovative new therapies and those that are similar to medicines already on the market, explains Mike Lanthier, operations research analyst on the economics staff of FDA’s Office of Planning. While all NMEs offer some therapeutic advantage, those that are “first-in-class” and “advance-in-class” medicines represent important advances, he explains. Alternatively, “addition-to-class” therapies may provide useful options for patients, but not substantial advances over existing products. And it is this last category that has experienced the much-hyped decline in approvals in recent years, while more vital therapies are holding steady or increasing in number, Lanthier points out in an FDA Voice blog posted Aug. 6, 2013. This “more nuanced and informative” assessment of NME categories thus refutes fears of an “innovation gap” that threatens drug discovery.

One factor may be a rise in small biopharma companies developing more innovative drugs, while large drug companies have focused on refining blockbuster drugs for large patient populations. NMEs from small companies have increased notably since 1996 and now account for 50% of approvals, compared to roughly one-third in the past, Lanthier and colleagues explain more fully in an article in the August 2013 issue of Health Affairs.

FDA initiatives also may support these developments. Most innovative NMEs have benefited from priority review treatment, and the new breakthrough drug program and added incentives for new antibiotics and pediatric treatments promise to expedite the development of innovative therapies. It’s also possible, the authors say, that the increased influence of large pharmacy benefit management firms reduces reimbursement for pricey drugs that lack proven benefits.

Another measure of biopharma innovation may be the number of new drug applications filed with FDA, although the quantity-over-quality measure also may apply here.

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