Is Your Quality Management System Ready for Fast Tracked Pandemic Related Drug Approvals?

By Mike Hidock, Director of Quality and Compliance Services, IQVIA

A New Drug Application (NDA), designed to prove that a drug is safe and effective for its intended use in the population studied, is the most traditional pathway taken with the FDA to deliver a drug to market in the U.S. Under this pathway, a drug developer with evidence from its early tests and preclinical or clinical research that a drug is safe and effective for its intended use can file an application with the FDA to market the drug. The FDA review team thoroughly examines all submitted data on the drug to make a decision to approve or not to approve it. This can take months or a year or more to achieve approval status.

But what the medicines produced are needed urgently? This is the reality we are living in as the COVID-19 pandemic continues to present a great number of challenges. Many companies have been working on a vast array of COVID-19 related devices and medicines, such as ventilators, vaccinations, respiratory medicines, and at home diagnostics, to join the fight against the spread of the virus. The FDA has pathways in place that support the expedition of normal review processes of an approved marketing application before a product is transported or distributed across state lines. This process is known as an Investigational New Drug (IND) application. The FDA has three different types of IND filing categories (Investigator, Emergency and Treatment) that fall into two main classifications (Commercial or Research).

Given the current climate, there has been a huge increase in the number of IND filings. According to the FDA, in Q4 2019 the total number of commercial, research, and emergency INDs and investigational device exemptions (IDEs) received by the FDA was 274. In Q3 2020 (post pandemic) that number catapulted to 2,769.

Following the initial approval of clinical data, FDA officials conduct routine inspections of drug manufacturing facilities across the United States, and abroad if approved products are manufactured overseas. Manufacturers may be informed of inspections in advance, or the inspections may be unannounced. Inspections may also be routine or caused by a particular problem or concern. The purpose of these inspections is to make sure that developers are following good manufacturer practice. FDA can shut down a facility if minimum standards are not met.

Many companies on the frontlines of combatting COVID-19 are household name big pharma companies, but the vast majority fall into the range of small to midsize companies that are completely virtual. While significant time and effort are spent by these companies on evidence from preclinical to Phase 3 trial data to gain FDA approval, they have historically put less emphasis on post market approval and their foundational Quality Management System (QMS).

The right time for considering the proper build-out of a QMS should be simultaneous to the development work for the associated drug or device; however, many companies overlook this and do not examine their QMS until much later in the process, if at all.  As a result, many companies will be facing FDA actions such as Form 483 findings that can lead to a Warning Letter situation. Since most COVID-19 products are not yet fully approved but authorized for emergency use, a quality issue could quickly take those products off the market and render them unusable to help bring an end to the pandemic. To mitigate the chances of this, companies should evaluate their pre-commercial readiness for quality management, focusing on four main factors: 

Readiness for Commercial Manufacturing

Determine whether the establishment(s) have a QMS that is designed to achieve sufficient control over the facility and commercial manufacturing operations. QMS Documentation (procedures/policies etc.) are to be in place prior to commercial manufacturing to support such control.

Conformance to Application

Verify that the formulation, manufacturing or processing methods, and analytical (or testing) methods are consistent with descriptions contained in the Chemistry, Manufacturing and Control (CMC) section of the application for the batch (and other pivotal clinical batches, when applicable), the proposed commercial scale batch, and the active pharmaceutical ingredient(s) (APIs).

Data Integrity

Audit the raw data, hardcopy or electronic, to authenticate the data submitted in the CMC section of the application. Verify that all relevant data, such as stability and batch data, were submitted in the CMC section. Center for Drug Evaluation and Research (CDER) product reviewers must be able to rely on the submitted data as complete and accurate.

Supplier Management

As a virtual company, it is crucial that all suppliers of materials, contract manufactures and packagers testing laboratories, etc. are properly qualified by the standards set in the company’s supplier management program. Additionally, each qualified supplier and the company must have a binding Quality Agreement in place to establish each party’s manufacturing activities in terms of compliance to current Good Manufacturing Practice (cGMP).

This is perhaps the most overlooked area in preparation for commercial manufacturing, most likely because it’s the right fit from a business perspective but fails to understand the compliance aspects of their contract partners.

The pandemic has shown once and for all that life sciences quality management is much more than complaints management. As COVID-19 continues to pose a threat to human health, INDs are unlikely to go away, particularly with the promise of COVID-19 booster shots to fight emerging variants of the virus. The speed and agility required of the pharmaceutical industry to ramp up pandemic related treatments requires holistic preparedness for quality management. By taking the time to equip their QMS, organizations ensure that they can maintain compliance and be part of the solution to save countless lives from the continued threat of the pandemic.