When drug or device manufacturers apply for marketing approval of a new product, the FDA may conduct a pre-approval inspection (PAI). The PAI is performed to help the Agency assure that a manufacturing facility named in an application can manufacture the product, and that the submitted data are accurate and complete. Ultimately, the purpose of the PAI is to make sure that the facility is in compliance with FDA’s rules and regulations.
Investigators want to know that the product was developed appropriately and the current good manufacturing practices (cGMPs) are up to FDA’s standards. Before visiting a production facility, the Agency’s investigator will review the Sponsor’s application. When the investigator arrives, they will compare the information in the application to what they find at the facility.
The Sponsor’s overarching goal is to receive a positive report; and an inspection that ends with a negative report can cause major delays in marketing the Sponsor’s product and result in loss of revenue and damage to the organization’s reputation.
To secure a successful PAI, it is helpful to take a proactive approach. Here are some of the steps Sponsors can take to ensure their medical device, software, or drug is ready for a PAI.
Sponsors receive advance notice of when a PAI will take place, giving them time to prepare a PAI Management Plan. Essentially, the management plan should spell out all the procedures the Sponsor’s personnel will follow during an inspection.
The plan should provide for:
It’s not an overstatement to say that a Sponsor’s product development program lives or dies by its documentation. Sponsors must establish and follow quality systems to help make sure that their products consistently meet applicable requirements and specifications.
For a medical device, it is crucial that you have a design history file (DHF) in place. According to 21 CFR, Part 820.30, the DHF shall contain or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and FDA quality standards. Sponsors must include or provide a reference to all records related to the activities completed during the design and development process. This includes all the user needs and design inputs developed at the start of the project as well as all the design outputs generated to build the device.
For a drug, cGMP is governed by 21 CFR, Part 211. Essentially, records shall be maintained for all drug products, components, drug product containers, closures, and labeling so that the data therein can be used to evaluate the quality standards of each drug product to determine the need for changes in drug product specifications or manufacturing or control procedures.
A Sponsor’s manufacturing process must be robust and the Sponsor must have documentation to prove its robustness. Demonstrating this involves showing that a Sponsor’s manufacturing process is as the Sponsor intended it to be for the marketed product. Validation is defined as the collection and evaluation of data from the process design stage through commercial production. Validation data establishes that the process is capable of consistently delivering quality product.
Effective validation contributes significantly to assuring product quality and that safety and efficacy are designed and built into the product. Ultimately, this means that when a Sponsor manufactures a product, all process-related risks have been mitigated and the finished product is at a reliable level of quality and consistency relating to identity, strength, quality, purity, and potency.
Internal audits are a key element of a quality system. The objective of an audit is to evaluate activities and documentation to ensure compliance to regulations and internal procedures. They are helpful when preparing for external inspections because Sponsors can identify quality deficiencies and remediate them prior to the external inspection.
Internal audit reports are not typically viewed by FDA inspectors, but it is a good idea to keep any records related to deficiency remediation ready for review. Those records simply support your maintenance of a robust quality system.
The personnel who will be taking a large part of the responsibility for getting through a PAI should be properly trained. They need to have knowledge of the processes that have been established as well as the supporting documentation that FDA inspectors will look at during the PAI. In essence, the personnel must be ready and capable of responding effectively to the challenges presented by an inspection. Conducting internal audits is an excellent way to prepare these personnel.
Preparing a product for pre-approval inspection starts with getting supporting documentation in order prior to the submission of a marketing application. This is where ProPharma Group can be your first line of defense. As your submission consultant, we will review all relevant documentation and work with you to develop a submission which balances risk, speed to approval, and cost.
Additionally, it is important to have an objective third party evaluate your quality system prior to an FDA inspection. Our quality and compliance services include mock audits that are designed to fit your specific situation. To learn more about how ProPharma Group can help with all your quality and compliance needs, contact us today.
April 28, 2016
Founded in 2007 by James Park and Eric Friedman, Fitbit Inc. launched its first activity tracking device in 2009. The device was called the Fitbit Tracker and it worked by tracking a number of...
October 1, 2015
FDA released proposed regulation that would allow sponsors to determine if their product is a drug/device, or if it is not a drug/device. Last week, the Agency announced a proposed rule “to provide...
February 28, 2019
On Tuesday, February 19th, FDA published a draft guidance for medical device makers which identifies a process for companies to request nonbinding feedback on certain FDA Form 483 deficiencies noted...