FDA Generic Drugs Office Advances QbD, Review Processes and QM System in Anticipation of User Fees

FDA's Office of Generic Drugs (OGD) is making significant strides forward in its efforts to implement quality by design (QbD), refine its review processes and implement a quality management system, in anticipation of the resource underpinning that user fees will provide.

On the QbD front, OGD has developed two case studies providing insight into what the office is looking for regarding oral solid immediate release (IR) and modified release (MR) dosage forms, respectively.

The office held workshops in conjunction with the Generic Pharmaceutical Association (GPhA) focused on the examples and their refinement in May 2010 (IR) and May 2011 (MR). The release of refined drafts of the two examples for comment and further discussion with industry is expected shortly.

Reviewer training on QbD is ongoing and another round of workshops with industry is planned for later this year. QbD training was held this past fall for the office's CMC leadership, which reviewed the potential revisions to its question-based review (QbR) system. Further training for CMC reviewers is anticipated during this spring.

Catalyzing a multifaceted effort to improve generics office review processes was a four month study by the consulting firm McKinsey completed in the spring of 2011. The OGD study followed in the wake of a McKinsey report prepared for FDA in 2009 on QbD uptake, challenges, and its potential impact on industry and regulatory processes (link provided below).

In response to the study, OGD has developed a four-pronged effort to refine and streamline its processes. The initiatives are addressing:

  • tightening the filing criteria to delimit the extra workload and time involved in remedying problems in
    the applications later when they are under review
  • implementing cross-discipline review and project management teams to better coordinate the flow of
    applications through the approval pipeline and facilitate a tracking dashboard
  • separating out the active pharmaceutical ingredient (API) drug master file (DMF) review from the drug product review to allow more specialization and better accommodate the tight generic drug user fee act (GDUFA) API/DMF goals, and
  • the increased use of complete response (CR) letters and other communication tools to assure the clarity and transparency of application status and deficiencies as called for under GDUFA.

The quality management system that OGD is developing calls for improving the documentation and clarification of procedures and their consistent application across the different office divisions toward achieving the efficiencies that GDUFA is mandating.

User Fees Will Impact Both Reviews and Inspections
The user fees themselves will provide additional resources for creating efficiencies in all aspects related to the review and inspection of generic drugs across the pre and post-approval spectrum. Aggressive timelines are set for achieving the agreed upon goals.

The implementation process will stretch across five years. The DMF objectives come into play during the first year, and the larger ANDA components gel in three-to-five years out after the hiring and training of the additional office staff needed to realize them.

The target at the end of the five-year period is basically to clear the backlog - now at around 2,000 applications and 3,500 supplements that have not met the stipulated 180-review timeline - and to complete the review of new applications within 10 months of receipt.

The number of ANDA receipts has plateaued since steadily climbing to around 900 in the years prior to 2007. OGD is estimating that the inflow will remain at about that level going forward.

During fiscal year 2011 (that ended September 30, 2011), OGD approved 457 ANDAs and granted tentative approval to another 136.

Reporting on the ANDA review accomplishments for the year at the annual GPhA/FDA Fall Technical Conference in October, Office of Generic Drugs Acting Director Keith Webber noted that the number of approvals was significant "given the staff that we currently have in the office and the complexities of the products that we receive."

Of particular significance, Webber emphasized, was the 106 approvals of "first generics" and 29 tentative approvals of products not yet off patent. These first generics are "in a class of their own in many regards," he commented, "because they are the ones that really spearhead the availability of generic drugs to the public."

Webber reviewed the 11 blockbuster drugs that are coming off patent in FY 2012 (see box below) and noted that nine of them were already tentative approved. For these important products coming to market, he said, "the reviewers and staff in the office have been fantastic at getting ahead of the game - making sure that those products are going to be ready to go once the patents run out. I think this shows the dedication that the staff has towards making sure public health is number one in their jobs and their achievements."

To read the complete story, please see the ECA website members' area.

Source: This article is taken from the IPQ (International Pharmaceutical Quality Journal).
IPQ's monthly format keeps subscribers "Inside the Global Regulatory Dialogue"™ where the initiatives are being defined that will reshape the landscape. The IPQ is one of the most important Journals in the GMP and regulatory environment. In co-operation with IPQ the ECA publishes selected articles in the members' area on the ECA website. Members also benefit from a special agreement with IPQ´s Editor in Chief Bill Paulson: an exclusive subscription fee for the IPQ Journal. You will find more information in the members' area.

To find out more about IPQ, please visit the IPQ website.

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