FDA Responsibility –  Is there inspectional approach differences for International companies by FDA ?

Most can agree that regulating the safety and effectiveness of drugs and medical devices is for the protection of public health and we applaud the regulatory agencies who work tirelessly to make this possible.

Our company has participated in many inspections with our India clients . We also have many clients in the US and Europe. One of the fundamental questions that are often asked, are the inspection approach different in regulated markets vs other markets such as India and China. We had our team who has participated in dozen(s) of inspections compare the inspectional approach.

We will use India as the example, but can be replaced by any other non-regulated market companies.

FDA Inspectors

The FDA inspectors are knowledgeable and follow very rigorous process during the inspection. They follow very specific guidelines and in most cases check for all six systems. The systems are described in FDA audit approach they are : Quality, Materials, laboratory, manufacturing, Facilities, label and packaging and if you are a biosimilar company they also will also cover R & D (process and analytical development).

USA, EU & India – FDA inspectors are assigned across the globe. Expect similar inspectors to participate in both US and International companies

Data Integrity Approach

US and EU – Cursory checks on all the systems to test the controls and if nothing is found they most likely stop.

India – Full deep dive on the first day, continued with a deeper dive the next and even deeper dive the following. There is a pre-conceived notion that based on the historical inspections India companies are hiding or taking short cuts when it comes to data integrity. The level of detail during the inspection is excruciating and the intensity could be cut by a knife. Both management and the analyst or operators should expect their honesty to be questioned at every path.

The inspectors come already loaded with expertise to diagnose the system and most cases know more about your system them your administrator. If there is something that is amidst, they will sure find it.

Lesson: Data Integrity

Be prepared for a full assault on both manual and electronic systems. They will be scrutinized at what I call “ANT” level detail. The analogy if the ant has a tattoo in his rear end and does not match with what your system expect a serious observations or discussion. Full data integrity risk assessment should be conducted both retrospective and prospective. Be prepare to defend your assessment, deviations and CAPA as well as your quality decisions for products that were released prior to risk assessment

Facility and Equipment:

USA an EU : A facility walk-through is conducted with a focus on understanding people, material and waste flows. The inspector typically sticks to the pre-determined route establish at the opening presentation.

India : The inspector walk-through is conducted in a two part process.

Part 1: General Walk-through – What are you hiding?

Inspector will walk through every single room in your facility in all your buildings to ensure you are not hiding anything. This inspection can last 1-2 days and likely will be done in GMP areas and Non-GMP areas. Be prepare to explain cleanliness, paper work, working conditions, air conditioning, storage of laundry, conditions of your bathrooms, IT closets, stationary storage, printers in all areas and even how the grounds are maintained ( linked to pest control).

Part 2: Process Walk-through – Where are you hiding ?

The second walk-through of the process will focus on what is hidden in your drawers, what is inside your document rooms, what printers capability are disabled and a little about the process. Be prepare to discuss both the process and cleanliness of your area. Also, a second tier of data integrity is checked to ensure there is no undue pressure on the people on the ground from management to do the wrong things. The process will be looked at and reviewed with a fine-tooth comb. This type of walk-through may last half day and may not touch the process. Expect several other visits to the lab or manufacturing area throughout the process. The inspector again will visit every room, closet, utilities, shoe room, laundry and any other areas that have a door. Be prepare to discuss your cleaning process for all the areas including floors, ceilings, lighting, drains and equipment.

Material System:

USA and EU: Inspectors focus on the electronic control of the system. They evaluate procedures for managing and controlling labels. Additionally, they will look for container management and quality status controls. Also, they will look at the qualification process of suppliers. At the end of this process the inspectors will move to other areas of focus.

India and China: Opportunity for more data integrity assessment

The inspector will focus on understanding the traceability of the data. The control mechanism and audit trails of people who have access to changing quality status. The printing and managing of labels that are attached to container will be scrutinized. Be prepare to review your all your templates that exist for preparing internal labels. Ensure that all the labels are issued, signed and approved after they are affix by QA. The qualification of personnel who enter data and their security profiles will be scrutinized. Be prepare to conduct a full audit trace for key raw materials. They will ensure either the electronic system or manual system is fully traceable and no mechanism for falsification of data exist. If paper systems is being used be prepare to discuss all the printer capabilities and defend the quantity of copies that have been made on printer. Cleanliness and location of material will be inspected along with all the storage condition. At this point for any temperature control system be prepared to defend set points, alarms and their review by QA.

Summary for Part 1

The FDA inspection outside the US and Europe are very different and maybe due to recent experiences in countries like India and china which export a significant amount of pharmaceutical medicines to regulated markets. In some cases FDA has caught companies falsifying data, making multiple injections on tests and destroying original records. A better picture of this can be constructed by looking at FDA warning letters on https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm

Given the level of importance that some of these drugs have on the wellbeing of the patient, you may ask if this is a fair approach ? Our team believes that while this inspection may be construed as extreme vetting, they may be required to adjust company culture and establish high level of expectations.

Companies who successfully navigate through the FDA data integrity assault will benefit greatly as they strive to be global players in the market place. For those who fail this incredible test there are significant learnings that when apply can positioned company to survive the level of scrutiny that is sure to come if they want to market products in the regulated markets like USA and Europe.

Our company has both experts and proven methodology that may able to help if you have recently been audited in this manner. Preparation and conducting the appropriate prospective and retrospective assessment that are scientifically sound will play a role on how the inspector(s) view you’re their findings.

In the PART II of this post we will cover how the inspectors audited the Laboratory and Quality Systems. If you interested in obtaining a pre-publish post please contact me (details below)

As always I welcome your comments and if you need to get in touch with me please e-mail me [email protected]