Confused by the new FDA CDER Site Selection Model? Here’s what you need to know.
CDER – the U.S. FDA’s Center for Drug Evaluation and Research which regulates over-the-counter and prescription drugs – has altered their fixed minimum inspection routine. It now requires inspection of both domestic and foreign drug manufacturing establishments “in accordance with a risk-based schedule.” The FDA must consider a facility’s “known safety risks” when determining the inspection schedule.
This new Site Selection Model (SSM) allows the FDA to prioritize routine quality-based inspections (e.g., cGMP inspections). One of the SSM’s objectives is to create global inspection equivalency – in essence, sites with equivalent risk will face equivalent frequency inspections, wherever they may be located, and regardless of drug type (innovator, generic, OTC).
What is CDER’s SSM?
The Site Selection Model (SSM) prioritizes facility inspections by considering risks related to drug quality which could arise from violations of cGMP requirements.
Who Sets and Manages the SSM Schedule?
This is where things get a little complicated, but bear with me…
The CDER Site Surveillance Inspection List (SSIL), which prioritizes facilities for inspection, is produced by the Office of Surveillance (OS) in the Office of Pharmaceutical Quality (OPQ). The planning and carrying-out of inspections is performed by the Office of Regulatory Affairs (ORA). ORA is also the office which plans and conducts the inspections as assigned according to the SSIL. OS tracks the accomplished inspections and provides quarterly updates.
The SSM ranks sites by various risk factors. Higher-risk facilities are assigned for surveillance inspections.
How is this accomplished? The Office of Surveillance takes the current catalog of sites and applies risk factors and weights to produce site scores. The sites are then ranked by score to compile the SSM inspection schedule.
What Criteria does OS use to Prioritize Drug Manufacturing Facilities?
FDA CDER’s Site Selection Model evaluates a number of risk factors when determining how to prioritize inspections. These include:
- Facility type (e.g., manufacturer, packager, lab).
- Facility compliance history, inspection frequency and outcomes. This includes both FDA and foreign agency inspections (pursuant to section 809 of the FD&C Act, and also check out our FAQ post on the US-EU MRA), and the inspection history of foreign regulatory bodies deemed ‘capable.’
- Time since last surveillance inspection (or whether the site has previously been inspected).
- Information regarding recalls involving the facility.
- Patient exposure and product risks, including dosage form, route of administration, API load, therapeutic classification, etc.
- Other criteria as may be deemed necessary to allocate inspection resources.
Who Will the SSM Impact?
The CDER maintains a Catalog of Manufacturing Sites, which includes facilities that commercially manufacture finished pharmaceuticals, as well as in-process materials and APIs for use in human drugs.
There are a number of cases in which a firm’s facility may not be included in the site selection model, including:
- Sites in which the last inspection was classified as open, or final official action indicated (OAI), are removed from routine surveillance inspection planning. For example, in the case of an OAI, re-inspection is determined as part of the enforcement effort.
- Sites currently on Import Alert are removed from routine surveillance inspection planning.
- Newly-registered sites (or those without prior routine surveillance inspection) are typically inspected within 30 days (and/or as a for-cause assignment).
- Sites can also be removed from the SSIL by request of the ORA, and subsequent investigation & confirmation by the Office of Surveillance. An example of this type of removal from the inspection list would be a recent inspection performed after the SSIL was generated. In such a case, the facility would be removed pending confirmation that the cGMP inspection had been completed.
What are the Objectives of the Site Section Model Program?
The program’s objectives include determining whether inspected firms (e.g., sites, facilities) are operating in compliance with applicable cGMP requirements. Additional goals include:
In cases in which they are not in compliance, the program’s objective is to provide the evidence for actions to prevent adulterated products from entering the market (or – as appropriate – to remove adulterated products from the market and to take action against persons or firms responsible).
The program aims to help drug manufacturers by providing input during inspections which can improve their compliance with regulations.
There are some longer-term goals, as well – including gaining a better understanding of current practices among drug manufacturers in order to update cGMP requirements, regulatory policy, and guidance documents.
FDA Inspection Classifications
After a SSM inspection, the FDA determines if the areas evaluated are in compliance with applicable laws and regulations. The FDA uses one of three classifications:
- No Action Indicated (NAI): No objectionable conditions or practices were found during the inspection (or the objectionable conditions found do not justify further regulatory action)
- Voluntary Action Indicated (VAI): Objectionable conditions or practices were found but the agency is not prepared to take or recommend any administrative or regulatory action
- Official Action Indicated (OAI): regulatory and/or administrative actions will be recommended.
Better Outcomes, With Lower Risk
This new inspection model holds the hope of creating a new common denominator for drug manufacturers, while improving the overall safety & compliance of those facilities manufacturing human medicines. It shines light on potential manufacturing deficiencies, and takes steps to ensure safer, more efficacious medicines reach the market.