Life Science Compliance Update

October 06, 2017

FDA Releases Draft Guidance for Industry: Statistical Approaches to Evaluate Analytical Similarity


The FDA announced a draft guidance for industry titled “Statistical Approaches to Evaluate Analytical Similarity”. The draft guidance offers advice to biosimilar sponsors on the evaluation of analytical similarity of a biosimilar to its reference product. FDA says this type of evaluation is performed as part of the biosimilar approval process to support a demonstration that the proposed biosimilar is highly similar to a reference product.

The draft guidance describes “the type of information a sponsor of a proposed biosimilar product should obtain about the structural/physicochemical and functional attributes of the reference product, how that information is used in the development of an analytical similarity assessment plan for the proposed biosimilar, and the statistical approaches recommended for evaluating analytical similarity.”

The draft guidance released is part of a series of guidance documents that FDA is developing related to the biosimilar approval process. Comments on the draft guidance are due to FDA within 60 days; on or around November 22, 2017. All submissions received must include the Docket No. FDA-2017-D-5525 for “Statistical Approaches to Evaluate Analytical Similarity; Draft Guidance for Industry; Availability.”

Guidance Specifics

According to the FDA, the objective of this guidance is to assist sponsors in demonstrating, through an evaluation of the analytical similarity of the proposed biosimilar and reference product, that the proposed biosimilar and reference product are highly similar to support licensure under section 351(k) of the PHS Act. In general, an analytical similarity assessment involves a comparison of structural/physicochemical and functional attributes using multiple lots of the proposed biosimilar product and the reference product.

To address the challenges of conducting appropriate statistical analyses in the evaluation of analytical similarity, FDA recommends using a risk-based approach. This approach to the evaluation of analytical similarity consists of several steps:

  • The first step is a determination of the quality attributes that characterize the reference product in terms of its structural/physicochemical and functional properties.
  • In the second step, these quality attributes are then ranked according to their risk of potential clinical impact.
  • Third, these attributes/assays are evaluated according to one of three tiers of statistical approaches based on a consideration of risk ranking as well as other factors. However, some attributes may be important but not amenable to quantitative evaluation.

FDA recommends that the analytical similarity evaluation begin with an understanding of the structural/physicochemical and functional attributes of the reference product. Based on information obtained about these attributes during development of the proposed biosimilar, the sponsor should develop an analytical similarity assessment plan. A key component of this plan is the description of lots available for similarity testing.

In general, principles for evaluating analytical similarity should be assessed by using appropriate statistic methods to evaluate the analytical data. Methods of varying statistical rigor should be applied depending on the risk ranking of the quality attributes. Sponsors should develop an analytical similarity assessment plan that includes their proposed statistical approach to evaluation and then should discuss this approach with the FDA as early in the development program as feasible.

The final analytical similarity report, which should include the analytical similarity assessment plan, should be included when a 351(k) biologics license application is submitted. The development of the analytical similarity assessment plan is the topic of the first subsection of the guidance, followed by a discussion of FDA’s current thinking on the statistical methods to be applied for evaluation.

September 27, 2017

New AAFP President to Focus on Administrative Burden


Michael Munger, MD, recently assumed the role of president of the American Academy of Family Physicians (AAFP). During his opening speech, he spoke about the progress being made in moving toward a value-based care approach and the angst many members feel about the increasing administrative burden on their practices.

Prior to his role as president, Munger served on the board for three years. During those three years, he noted that a recurring theme in conversations with other family physicians was what can be done about the overload of administrative work that is taking time away from meeting with patients.

“You all love interacting with patients and being a part of their lives, but are drowning in the administrative complexity and nonvalue-added tasks we all face daily,” Munger said in his speech. “It's standing in the way of meaningful patient care. In fact, on the most recent member survey, administrative complexity was listed as the number one issue you need help on from your AAFP.”

Simplifying and streamlining administrative processes will be one of the AAFP’s strategic priorities under Munger’s watch. Munger notes that the AAFP has already begun pushing for changes with prior authorizations, interoperability and documentation guidelines. Efforts to reduce administrative burden would do extend to board certification, with Munger arguing board exams and maintenance of certification shouldn’t be “used as a sole criterion” for employment or commercial payer participation.

AAFP will “continue to hound Congress, as well, that something must be done,” he said.

Munger also alluded to his planned work on administrative burden in his September 13, 2017, blog post, noting, “So, as I take the role of AAFP president today, I can relate to our members' individual circumstances and concerns, regardless of their practice setting. There is much work to do in the year ahead on issues such as payment reform, administrative burdens and more, and I'm honored to represent you.”

During a Q&A session, Munger was asked what topic he expects to be prominent during his presidential term. He responded with the following,

I know our members are quite frustrated with the administrative complexity that is involved in the day-to-day practice of medicine. Look at electronic health records; they were promised to simplify practice, but many physicians will tell you that has not yet happened.

Much of our members' angst is tied to paperwork such as prior authorization requests from payers and that endless flow of forms that need attention. Family physicians are looking for relief from that overall burden and from tasks that hinder rather than help them with hands-on patient care. The AAFP recognizes their concerns and is working hard to make things better.

The increased burden AAFP criticizes has often been blamed on the transition from volume to value, but when it comes to payment reform, Munger said he believes the industry is moving in the right direction. In his own practice, he said he’s seen payment that “reflects the delivery of comprehensive coordinated care.” He praised some CMS programs, like Comprehensive Primary Care Plus (CPC+) and the Quality Payment Program, though adding the later still needed some tweaks in its “overall complexity.”

"After much talk for years about the move from volume to value, I fortunately have finally started to see changes in my practice," Munger said.

September 25, 2017

FDA Guidances Being Issued Slower than Expected


We found an interesting Regulatory Focus story on the lack of FDA guidance documents since the start of President Trump’s tenure in office. FDA announced it intended to release more than 100 draft guidances in 2017 but has not been close to that amount. Recent guidances, to illustrate, can be found at the following link.

Unclear reason

Regulatory Focus speculates it could possibly be related to President Trump’s Executive Order aiming to reduce regulatory activity. Or, before Commissioner Gottlieb was confirmed, it may have been the lack of a top official at the agency. The answer from the administration is particularly interesting. Regulatory Focus wrote:

“The answers remain unclear. FDA referred Focus questions on the matter to the White House, which referred Focus to the Department of Health and Human Services and the Office of Management and Budget, which did not respond to questions.”

Some industries are patiently waiting for more FDA guidances, for example, on the Food Safety Modernization Act. However, we have seen guidances issued in several areas released in the month of August:

Identifying Trading Partners Under the Drug Supply Chain Security Act Guidance for Industry - Draft Guidance - 08/18/17

Expiration Dating of Unit-Dose Repackaged Solid Oral Dosage Form Drug Products - Final Guidance - 08/08/17

CMC Postapproval Manufacturing Changes for Specified Biological Products To Be Documented in Annual Reports - Draft Guidance -08/08/17

Child-Resistant Packaging Statements in Drug Product Labeling Guidance for Industry - Draft Guidance - 08/02/17

Antibacterial Therapies for Patients With an Unmet Medical Need for the Treatment of Serious Bacterial Diseases - Final Guidance -08/01/17

We will continue to monitor the trends of FDA guidance documents in the coming months as Commissioner Gottlieb continues to build his staff and direct the future of the agency.

As Regulatory Focus reported, Rachel Sachs, an associate professor of law at Washington University in St. Louis, is quoted as saying: “I think they're waiting for Gottlieb to set his priorities, and they'll move forward then. The other thing I'll say is that they've been busy behind the scenes on things like the -UFAs [user fee agreements], so I wouldn't be surprised if a lot of time has gone into that.”


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