By Robert Iser, Vice President, PAREXEL Consulting
There are many changes occurring within FDA with respect to inspection management, timing and communication expectations, tied to the recent agreement between CDER and ORA on a facility evaluation concept of operations (ConOps). This ConOps operating model applies to pre- and post-approval, surveillance, and for-cause inspections. The first update under the ConOps is to FDA’s compliance program for routine CGMP (surveillance) inspections [7356.002], implemented on 10/31/2017.
Major changes in the 7356.002 compliance program (found at the following FDA webpage link https://www.fda.gov/downloads/ICECI/ComplianceManuals/ComplianceProgramManual/UCM125404.pdf) related to roles and responsibilities for surveillance inspections and timing of communications from FDA to inspected facilities are summarized as follows:
- Office of Surveillance (OS) in CDER’s Office of Pharmaceutical Quality (OPQ) uses a risk-based site selection model to annually identify facilities for inspection, and prepares an up-to-date site dossier for each of the identified facilities in advance of a scheduled surveillance inspection
- Office of Regulatory Affairs (ORA)
- Schedules surveillance inspections for individual sites
- ORA leads surveillance facility inspections with CDER participation, based on the CPGM and quality information summarized in a site dossier
- If the initial classification is Official Action Indicated (OAI), ORA provides a written classification analysis, including the electronic documents, to the Office of Manufacturing Quality (OMQ) in CDER’s Office of Compliance (OC) within 45 calendar days of closing the inspection
- If the facility inspection results in an ORA recommendation for a No Action Indicated (NAI) or Voluntary Action Indicated (VAI) classification and no further action is recommended, ORA issues an decisional letter within 90 calendar days following the inspection closing
- Office of Manufacturing Quality (OMQ) in CDER’s Office of Compliance (OC)
- Makes a final classification for pOAI cases, with input from the Office of the Chief Counsel, and issues a decisional letter in 90 calendar days following the inspection closing (e.g. letter to a facility that they are OAI)
- If an inspection is classified as final OAI, OMQ, solely or in collaboration with ORA, takes an appropriate action within 90 calendar days of the decisional letter (e.g. Warning Letter)
- If an advisory or enforcement action is not warranted (i.e., classification downgrade), OMQ notifies ORA of the change in classification
These compliance program revisions have already been implemented and facilities that are currently being inspected will see FDA applying the timelines and responsibilities for site classification, after routine surveillance inspections.
Ensuring facilities included in regulatory submissions are in a state of CGMP compliance and timely responses to FDA inspection communications are crucial to assuring there are no delays in the review and approval of pharmaceuticals for patients to need them. PAREXEL Consulting’s dedicated subject-matter experts are uniquely suited to provide advice to sponsors developing products and preparing regulatory submissions, as well as, quality professionals managing manufacturing facilities on FDA’s expectations during routine surveillance and product specific (pre-approval) inspections. PAREXEL currently supports numerous clients in developing and implementing regulatory and compliance strategies to support submission new drug, biologic and generic products to the FDA.