FSMA Rules – Round Two

Signed into law in 2011, the Food Safety of Modernization Act (FSMA) is the most sweeping change to the way food safety is regulated in the U.S. since the adoption of the Food Drug and Cosmetic act itself in 1938. Due to the sheer size and magnitude of this legislation, the FDA is taking time to get the rules correct.

Many of us in the food safety industry had been asking when we would see the next round of FSMA rules. Originally, the FDA had planned to issue the next round of rules in early summer 2014, but the deadlines were again extended. Finally, on September 19, the FDA issued four supplemental proposed rules:

  • Proposed Supplemental Rule for Produce Safety
  • Proposed Supplemental Rule for Preventive Controls for Human Food
  • Proposed Supplemental Rule for Preventive Controls for Animal Food
  • Proposed Supplemental Rule for Foreign Supplier Verification Programs (FSVP)

The proposed supplemental rules were issued to address specific concerns raised in comments that the FDA received in response to the original proposed rules. They do not replace the original proposed rules.

While it is impossible to determine the exact dates when the final proposed rules will be issued, we do know that there are court-mandated deadlines for the FDA to release the final proposed rules. These dates are as follows:

  • August 30, 2015 – Preventive Controls rules – both the human food and the animal food rules
  • October 31, 2015 – Produce Safety, Foreign Supplier Verification Program, Accreditation of Third-party Auditors
  • March 31, 2016 – Sanitary Transport
  • May 31, 2016 – Intentional Adulteration/Food Defense

While we wait for the final rules, there are some things you can – and should – be doing.

Be Prepared

First, make sure you are prepared by utilizing the proposed rules that have already been published. While the specific details of each final rule are still unknown, the proposed rules provide a solid direction and basis of the requirements. Most likely, your customers will begin holding you to the standards of the proposed rules before the FDA finalizes and enforces the final rules.

Focus on Minimizing Risk

Second, begin building a good case around how your company is considering potential hazards, as well as the programs you are implementing to minimize risk. It is already determined that the FSMA rules will require more testing, however, the programs and controls companies use to verify testing is also an important component.

Get Your Comments In

Lastly, let the FDA know what you think of this second round of proposed supplemental rules. You have been given until December 15, 2014 to comment, so take the opportunity to influence the final outcome.

For more information and updates on FSMA, visit their website.

Harmonizing Anatomic Pathology and Histology Services: Constructive Steps Toward Greater Precision in Global Oncology Trials

Zemanta Related Posts ThumbnailIn 2013, oncology represented the largest segment of the clinical trial market. In 2014, it is estimated to grow by 4.9%,1 reaching nearly $100 billion. The number of oncology clinical trials stands well above those in other therapeutic areas and most major biopharmaceutical companies are involved in oncology to some degree.

Yet, with such compelling numbers, why do only 6.7% of these trials lead to FDA approval from Phase 1?2 Possibly because of difficulties recruiting patients for oncology trials, but more likely due to the complexity of cancer as a disease. Continue reading

Your Customers and Your Market Access Are Changing!

Your Customers and Your Market Access Are Changing! - Covance BlogUS health care is exponentially more complicated today than just 5 years ago. Even the most competent, experienced marketing teams may not anticipate or clearly understand the complex forces that are changing how we select, dispense, and reimburse for drugs and devices.

Changes in Traditional Customers

Pharmacy Benefit Managers (PBM) are your primary contracting conduit into commercial and Medicare Part D plans to assure formulary market access. The FTC approved the $29.1 billion ESI-Medco merger, further consolidating the PBM group. If your new product is not granted preferential access on a national PBM, you may be losing access to 70 million patients. Continue reading

5 Uses for Muscle Biopsies in Early Research Studies

muscle-biopsyRunning along the side of your thigh, the vastus lateralis muscle works with three other muscles within your “quad,” permitting actions crucial for forward movement. In the laboratory, clinicians are also relying on muscles like the vastus lateralis to move their research forward in the study of neuromuscular agents.

Muscle biopsies hold the key to understanding many aspects about a potential treatment or therapeutic agent. From pharmacokinetics to stem cell therapy, there are several intriguing areas of interest in the field. Continue reading

FDA Takes Final Step On Manufacturing Standards of Infant Formula

FDA Takes Final Step On Manufacturing Standards of Infant FormulaAn estimated 1 million infants in the U.S. are fed formula from birth, and by the time they are three months old, about 2.7 million rely on formula for at least part of their nutrition.

On June 9, 2014 the U.S. Food and Drug Administration released a final rule regarding the manufacturing standards of infant formula. The final rule—which amends the FDA’s quality control procedures, notification, and record and reporting requirements for manufactures of infant formulas—is meant to ensure that formulas for infants without unusual medical or dietary problems are safe and support healthy growth. The rule also establishes current good manufacturing practices (CGMPs), and sets a date of September 8, 2014 for manufacturer compliance. Continue reading

Risk-Based Monitoring: Working Smarter, Not Harder

A six-step systematic, proactive approach to your study can help transform risks into returns

Risk-based Monitoring (RBM)Recently, the major regulatory agencies—FDA and EMA—have highlighted their concerns that current monitoring approaches are not only inefficient, but they also fail to support the overall integrity of the trial itself. In the light of recent regulatory guidances for risk-based monitoring (RBM), the industry is re-thinking the way clinical trials are conducted.

However, even before your study commences, the opportunity for RBM is present. By viewing your study as a holistic process—and by leveraging prior experiences and insights—you can more effectively manage risk while simultaneously optimizing quality. Continue reading

Simple Strategies for Balancing Risks in CNS Drug Development

neuroDrug discovery and development is inherently risky. Recent figures indicate that less than 11% of new pharmaceutical agents entering clinical development reach the marketplace across all therapeutic areas. For those working in CNS drug development, we know well that the prospect of seeing our compounds passing through all phases of drug development and successfully reaching the market is even more challenging.

This low success rate in CNS drug development has been attributed to a number of reasons, among them the complexity of the brain physiology, the limited characterization of the pathological mechanisms leading to neuronal dysfunction or the suboptimal knowledge about the mechanism of action of drug candidates by the time the compound enters clinical development. Continue reading

Reflections on the Placebo Response

placebo-responseSince the 1960s, much medical research has been conducted on placebo, an inert agent that does not contain any active therapeutic substances. It looks like a real medicine, but it is not; and it is used to diminish the suffering of the patient through expectation rather than through the exertion of a specific medical effect. Given the importance of this false drug in the treatment of psychiatric and neurological diseases, these investigations have become one of the most interesting and critical aspects of neuroscience. However, rather than placebo itself, it is precisely the placebo response, defined as the patient’s condition or symptoms resulting from placebo (natural history minus placebo condition), that has attracted attention. A problem exists for clinical trials in major depression, anxiety, neuropathic pain, or Parkinson’s disease arises when this placebo response becomes high enough that it’s impossible to differentiate between the true effect or clinical response of the investigational drug and the placebo effect itself.

The placebo response constitutes a paradox. While in clinical development, placebo responders are excluded or treated with special attention to minimize and keep under control their response to placebo. Continue reading

Biosimilars: The Commercial Challenge

acaconv 3721With the implementation of the FDA’s abbreviated biosimilar approval pathway, biosimilars have become one of the fastest-growing categories in the biopharmaceutical sector. While these lower-priced alternatives will offer value in terms of cost savings, many stakeholders have voiced concerns over switching to biosimilar products.

The Stakeholders

Three main stakeholders of market access will determine the commercial success of biosimilars:  payors, providers, and patients.

Despite potential cost savings, many payors may be reluctant to aggressively steer utilization toward these agents until they have compelling data to demonstrate safety and efficacy profiles comparable to those of innovator products. Continue reading

Is There a Case for Open-Label Extensions to Early Development Studies?

Balancing the need for early access to treatments for rare disorders and protecting patients’ safety and the viability of promising novel treatments

NeuroScience_email-header-imageOver the past 10 years, I have been asked to provide advice on whether or not to provide open-label, long-term treatment with novel drugs during early development. I had followed the orthodoxy to not offer such treatment until some demonstration of beneficial effect and robust preclinical safety data are generated. However, our understanding of acceptable risk in the context of diseases with high unmet medical need is changing. I recently was involved in such a case in which an open-label extension for a phase 1b study seems to make sense.

Examples of patients’ growing influence are the Patient Focused Drug Development Initiative (PFDDI), created out of the Food and Drug Administration Safety and Innovation Act (FDASIA), which is directed to incorporate patient view point in the regulatory process. Several of the PFDDI 2014 meetings are relevant to my area of expertise, neuroscience: Fibromyalgia (March 26, 2014); Neurological manifestations of inborn errors of metabolism (June 10, 2014); Parkinson’s disease and Huntington’s disease (TBD). Another example is the collaboration between the FDA and the Duchenne Muscular Dystrophy patient community to advance useful regulatory tools for benefit-risk consideration in DMD (page 58). Similar efforts to incorporate patient input for orphan disease are underway in Canada. Formalizing consideration of patients’ preferences will likely have direct implications for determining acceptable risk when benefit is largely unknown and even the regulatory value of the data provided by open-label extension studies.

This shift has significant implications for biotech and pharmaceutical companies in various areas, such as ethical (eg, exposing patients to long-term risks with no extenuating benefit), legal (eg, liability for negative outcomes) and financial (higher drug production costs, implementation of longer trials). For those of us in clinical development there are also a number of significant implications, such as larger placebo effects because of higher expectations about treatment success, a decrease in the number of eligible patients, and conflicts with patients who want to continue on the drug even after blinded trials show no efficacy and development has been discontinued.

So what implications does this change in thinking have for future drug development? It means that compounds and patient populations appropriate for potential early open-label extensions need to do a lot more upfront planning and implementing. For instance:

  • Early engagement with the patient community
  • Fortification of natural history data
  • Acceleration of preclinical safety studies
  • Early vetting with Regulatory agencies
  • Robust inform consent development with external input
  • Development of a solid long-term plan for data interpretation to provide the reassurance needed to acquire adequate financial support.

To share your views on open-label extension studies and discuss the risks and benefits of an open-label extension study for your disease indication of interest, please contact us.