Final FDA Guidance issued supporting risk-based monitoring

FDA final guidance entitled “Guidance for Industry Oversight of Clinical Investigations —A Risk-Based Approach to Monitoring,”  was issued early August and is similar to the draft guidance published in 2011.  FDA encourages risk based remote monitoring, electronic tracking methods, and also defines that if a CRO is responsible for monitoring a study, the Sponsor should still review the CRO to ensure they are meeting regulatory and contract requirements. Zachary Brenna from notes in a recent article that this approach may be most appropriate for Phase II and IV trials, and, reviews some of the rationale as to why Sponsors may be slow to adopt this with pivotal registration trials.  To view Brenna’s article, click here and to read FDA’s final guidance, click here.   Need assistance with your clinical trial?  Contact us at for assistance with IRB reviews, protocol writing, development and execution of risk based monitoring plans, CRO audits, and more.

FDA issues new guidance document regarding drug supply chain

In 2012, President Obama signed the Food and Drug Administration Safety and Innovation Act (FDASIA, Public Law 112-144) into law. This Act has several important provisions that expand FDA’s authorities and strengthens the agency’s ability to advance and safeguard public health.

Section 707 of FDASIA adds 501(j) to the Food, Drug, and Cosmetic Act (FD&C Act) to deem adulterated and not acceptable for sale in the US any drug that “has been manufactured, processed, packed, or held in any factory, warehouse, or establishment and the owner, operator, or agent of such factory, warehouse, or establishment delays, denies, or limits an inspection, or refuses to permit entry or inspection.” (1)

On July 14, 2013, a draft guidance implementing penalties for manufacturers who delay inspections or deny access to inspectors was issued by FDA. (2)  The guidance defines the types of actions the FDA will consider to be “delaying, denying, or limiting inspection, or refusing to permit entry or inspection”.  These include:

  • Delay of inspections (i.e., delay scheduling pre-announced inspections, delay during an inspection and/or delay producing records);
  • Denial of inspection;
  • Limiting of inspection; (i.e., limiting access to facilities and/or manufacturing processes, limiting photography, limiting access to or copying of records, limiting or preventing collection of samples); and
  • Refusal to permit entry or inspection. (2)

An additional authority provided by FDASIA is section 709.  Section 709 amends section 304(g) of the FD&C Act (21 U.S.C. 334(g)) to provide FDA with administrative detention authority with respect to drugs. Section 304(g) of the FD&C Act, as amended by FDASIA, provides FDA the same authority to detain drugs that section 304(g) already provides FDA regarding tobacco products and devices.

Protecting the global drug supply chain and making sure that patients have access to the drugs they need is a priority for FDA.  As nearly 40% of finished drugs are imported and nearly 80% of active ingredients come from overseas sources,(3)it is important that FDA is provided the additional tools it has been seeking to better meet the challenges of regulating a global supply chain. FDASIA is an important regulatory development that enables FDA to better regulate the safety of the drug supply and to combat the trade of counterfeit and adulterated drugs.

Need help navigating FDA inspection or issues with API vendor management?   Contact us at


  1. Food and Drug Administration Safety and Innovation Act Section 707. Accessed 12 August 2013.
  2. Guidance for Industry Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection. Accessed 12 August 2013.
  3. Public Meeting: Implementation of Drug Supply Chain Provisions of Title VII of FDASIA. Accessed 12 August 2013.




Breakthrough designations at the top of Pazdur’s priorities Matthew Herper describes the distorted image of the director of the FDA’s Oncology and Hematology Products, Dr. Richard Pazdur, as the villain to cancer treatments by his critics.  In an interview he gave at the annual American Society of Clinical Oncology, the portrayal shifted to his reality, his standards, and pushes to bring cancer therapies to the public. Pazdur commented about the rising amounts of cancer drugs approved, “We don’t have a lot of questions on drugs because they’re slam dunks. It’s not if we’re going to approve them. It’s how fast we’re going to approve them.”  Quick approvals are also being aided by a new “breakthrough” designation, which was spurred by the FDA Safety and Innovation Act of 2012. The new breakthrough designation applies to treatments for life threatening diseases such as various forms of cancer. The breakthrough designation is different than some of the other accelerated process designations because it allows the companies to call in more times and get a clear schedule to work with the FDA. Pazdur claims that there must be a difference in communication level for the entities that receive the breakthrough status, otherwise it is worthless.  For the full article click here.

Bowker leads FDA supplier audit webinar

Are you a supplier of raw materials, component parts or finished product to biopharma or medical device companies? The supply chain for pharmaceuticals, biologics and medical device companies are increasingly being audited by their clients and FDA.  On July 25, 2013, Pearl Pathways’ own Gretchen Bowker will lead a webinar on FDA audits discussing the best practices and provide practical tips to prepare for FDA audits, as well as client audits. The webinar will be held through

Where: Register here.

Fee: $199.00

When: July 25, 2013

Duration: 60 minutes

For more information and registration click here.

FDA takes action against websites selling unapproved drugs

Christopher Kelly reports on that The U.S. Food and Drug Administration (FDA), in partnership with international regulatory and law enforcement agencies, took action this week against more than 9,600 websites that illegally sell potentially dangerous, unapproved prescription medicines to consumers. A motivating factor behind the action was the 6th annual International Internet Week of Action (IIWA), a global combative against the online sale and distribution of illegal and counterfeit medicines. One piece of this year’s campaign was Operation Pangea VI, which used the FDA’s Office of Criminal Investigations partnering with the US District Attorney’s Office to seize and shut down almost 1,700 illegal online operations. The effort running from June 18 to June 25, 2013 targeted illegal sites using large brand names and “FDA approved” labels to sell non approved drugs that look similar to Avandaryl, Celebrex, Viagra, Levitra, and Clozaril. The aim of this effort is the protection of citizens against illegal medical products. How much emphasis do you think the FDA should put into this initiative? For the full article, click here.

Rate of FDA inspections not slowing

FierceMedicalDevices’ Damian Garde shares that the amount of medical device inspections under President Obama’s terms has skyrocketed up 47%, hitting eight year highs.  The number of warning letters handed out by the FDA is correlated with this growing number as well. The growing rate of inspections and warning letters does not seem to be slowing; the agency is requesting $870 million to run the Center for Devices and Radiological Health next fiscal year. It is also clear that the agency is targeting manufacturing processes, making up 60% of the warning letters handed out. While the rest was split between design, management, and document control. How large of a role do you think the FDA should play in inspections? Read the full article here.

CMO quality agreements highly recommended by FDA

Zachary Brennan of reports that the US FDA is recommending the usage of written quality agreements by pharma companies and CMOs. Although the FDA does not require such documents under cGMP (current good manufacturing practices) regulations; parties that have not complied with the recommendation have been issued warning letters.  By definition the FDA says a written quality agreement is a document outlining the responsibilities for the owners of the drug and the CMO in terms of the basic cGMP regulations. Most of these documents follow a standard form of:

  • Purpose
  • Terms (effective date and termination clause)
  • Dispute resolution
  • Responsibilities, including communication mechanisms and contacts
  • Change control and revisions

The FDA is also offering case studies for situations where a quality agreement does not exempt a CMO’s facility from cGMP requirements. Overall, The FDA is using written quality agreements to reduce the likelihood of misinterpretation and error from the manufacturing process. Read the full article here.

Could FDA committee voting be influenced by seating location?

In an article posted by, Stefanie Koperniak describes a new paper written by Christopher L. Magee, professor at MIT, and David Broniatowski, professor at Johns Hopkins University. The paper, “Does Seating Location Impact Voting Behavior on FDA Committees?” will be published in the July issue of The American Journal of Therapeutics, and will analyze that very question.  Both authors believe that although panels should reflect objectivity, there is still a human nature component. Do you think that seating location can have such impact? Read the full article here.

New diagnostic test regulations may be in the future

Matt Herper, of Forbes, reports that FDA Commissioner Margaret Hamburg,, announced the FDA will be taking new steps to enforce regulations against certain diagnostic tests during her speech to recognize Richard Pazdur for his efforts in approving cancer drugs,. She says, “Advanced diagnostics such as these are the cornerstone of personalized medicine, and their development can only foreshadow the many advances on the horizon.” Hamburg accompanied that statement by revealing that not all diagnostic tests are made to perform at that level. LDT’s, or laboratory developed tests, are produced and used in the company’s own facilities but can be marketed without FDA premarket review. This was not a problem in the past because of the simplicity of the LDT’s, but now as they are becoming more complex the FDA is taking a greater interest. Hamburg’s speech did not discuss any specifics about future regulations and standards, but it is safe to say companies have heard the message she sent. Do you think new regulations will be beneficiary for diagnostic tests and LDT’s? Read the full article here.

St. Vincent Health Research Symposium to be held June 12th at the Marten House

The St. Vincent Research and Regulatory Affairs will be hosting the 9th Annual St. Vincent Health Research Symposium next month. This daylong event will feature keynote speakers, William Droegemueller, MD, Distinguished Clinical Professor, Obstetrics and Gynecology at University of Colorado Medical School and Delia Wolf, MD, JD, MSCI, Assistant Dean, Regulatory Affairs & Research Compliance Director, Human Research Administration at Harvard School of Public Health.

The symposium will include both scientific and regulatory educational opportunities, and will highlight the Symposium Abstract Competition winners.


Fee: No fee for St. Vincent associates and Ascension associates. There is a $95.00 fee for general public.

When: Wednesday, June 12, 2013

Time: 7:00 AM – 5:00 PM (Continental breakfast and lunch included)

Where: Lilly Conference Center at the Marten House

1801 W 86th St., Indianapolis, IN 46260

For more information call (317) 388-2194 and to register click here