A previous blog entry addressed the Office of Pharmaceutical Quality ‘One Quality Voice’ effort, an aspirational view of FDA’s efforts to ensure coordination in the review, inspection, and approval process as well as post-approval oversight of both facilities and products. Shortly after that publication, FDA’s Office of Product Quality published their first annual report that we address in this blog entry.  

Introduction

The introduction section provides some history of the challenges and successes of OPQ. Challenges this year have included:

  • Severe hurricanes, particularly those in Puerto Rico, that have impacted drug and device manufacture and distribution.  
  • New product types and technologies were approved for the first time in 2017 including CAR-T products and gene therapy to name a couple.
  • The opioid abuse epidemic and FDA’s efforts to ensure that new opioid products are abuse deterrent or abuse resistant.  

Among the successes for 2017 was:

  • The Mutual Recognition Agreement signed with the EMA that will permit both agencies to focus inspection resources on high-risk areas and minimize duplicative inspections of sites.
  • FDA approved 132 new drug applications including 13 with breakthrough therapy designation, 21 BLAs including 7 with breakthrough therapy designation, and 5 biosimilar products.  
  • FDA also approved just over 1,000 ANDAs of which 150 were priority first generics.

A busy and successful year on the approval front. The introduction section also provides a graphic representation of the OPQ structure and organization, something that may also be found in the ‘One Quality Voice’ whitepaper.

The annual report also provides a listing of objectives and key initiatives from 2017 on page 5 and includes:    

  • Emerging Technologies
  • Concept of Operations for Facility Evaluations and Inspections (ConOps)
  • New Inspection Protocols Project
  • Knowledge Aided Assessment and Structured Application
  • Enhanced Core Work Functions

Let’s pick a couple of the areas and look at accomplishments from 2017:

  • One of the areas where FDA made significant progress was in the “concept of operations“ (ConOps) development and implementation. 
    • CDER and ORA reached agreement on roles and responsibilities for the various types of GMP inspections. FDA published the signed agreement in June of 2017 and revised Chapter 56 of the Compliance Program Manual (7356.002) Drug Manufacturing Inspections to align with the revised inspection responsibilities.
  • A second area addressed is the New Inspection Protocols Project.
    • In 2017, FDA initiated a third pilot for NIPP inspections at sterile drug process facilities and developed a plan to expand this to additional dosage forms.  

However, even with all of these accomplishments, what seems to be missing in both this publication and in the “One Quality Voice” publication is a clear description of what success ‘looks like’ and how FDA will know they have met the aspirational goals identified. I’ve not seen much, if anything, published regarding the outcome of the first two NIPP pilot efforts and the changes that were made to refine the effort. Personally, I’d like to know what the FDA felt worked well (and why) as well as what they modified in the subsequent pilot efforts.

FDA is also enhancing their global reach by partnering with other health authorities. FDA now recognizes inspections performed by twelve EU health authorities and will complete evaluation of the other countries by mid-2019. The health authorities that FDA recognizes as conducting facility inspections that meet FDA requirements include:

  • Austria
  • Croatia
  • France
  • Italy
  • Malta
  • Spain
  • Sweden
  • UK Greece
  • Hungary
  • Czech Republic
  • Romania

The European Commission determined that FDA inspections are equivalent to those of the EMA and have eliminated 130 sites from their inspection plans for 2018 as a result. This Mutual Recognition Agreement will allow both health authorities to leverage limited resources and global manufacturing sites to focus on areas of highest risk. It will be interesting to see metrics in a few years regarding how many previously duplicative inspections each authority has been able to eliminate and where those resources were allocated.

Page 8

Here we have lists of guidance documents (both draft and final) that were published in 2017. All but two were published in the last half of the calendar year 2017. FDA also published a variety of MAPPS and all but one were published in the last quarter of the year.  

FDA’s efforts at continuous improvement and operational excellence focused on internal activities and included the development of Standard Operating Procedures (SOPs) that supported both core business processes and implementation of the User Fee Programs. The Learning and Professional Development branch at FDA was busy developing and delivering courses/seminars focused on scientific and regulatory areas of staff development. OPQ also provided opportunities for staff to visit pharmaceutical companies in the US to learn about drug development and manufacture.

Pages 11 and 12

Here, the FDA provides a variety of figures addressing drug approvals for both original applications (NDA, ANDA, and BLA) and supplements. Among these activities were ANDA assessments that were expedited in consideration of potential drug shortages.

Page 14

Here is a graphic of pre-approval and post-approval facility inspections conducted in 2017. These figures do not include the routine surveillance and for cause inspections that take up most of the GMP inspection efforts of FDA. Finally, FDA is working on their plan to inspect “all previously uninspected sites (foreign and domestic) by the end of FY2019” (September 30, 2019).  

FDA’s research efforts address five areas including:

  1. Pharmaceutical analysis and characterization
  2. Manufacturing science,
  3. Immunology
  4. Tumor biology
  5. Infectious disease and inflammation

The Agency is expanding their programs to include 3D printing, continuous manufacturing, and emerging technologies.

At the end of this report…

FDA says “In early 2018, OPQ will roll out a 2018-2022 Strategic Plan which will include strategic priorities, objectives, and performance goals over a 5-year period.” I look forward to this, and we will address it when it is published.

I would ask FDA to include clear measures of success, along with measurable interim goals. Industry and the FDA are both well served when goals are clear, measurable, and time-bounded in their implementation with interim benchmarks along the way to their completion. FDA expects similar from the industry in response to forms-483 and other enforcement actions requiring corrective and preventive activities.