Improving U.S. Drug and Medical Product Quality: What Manufacturers Should Focus On

Elizabeth Miller, Pharm. D. — Elizabeth Miller, Deputy Associate Commissioner for Medical Products, Office of Inspections and Investigations

By Elizabeth Miller
Deputy Associate Commissioner for Medical Products
Office of Inspections and Investigations

As patients, we expect our medicines, vaccines, medical devices, and other life-saving treatments and products to be safe, effective, and of the highest quality. At the FDA’s Office of Inspections and Investigations (OII), it’s our job to make sure you and your family have access to products that meet such standards.

We do this through our risk-based oversight of industry, which includes, among other things, in-person inspections inside medical product facilities. Our regulatory inspections can result in the identification of issues that could otherwise threaten medical product safety and integrity.

As part of our commitment to transparency here at OII, I’d like to share some of our recent inspection data so that you—U.S. consumers, patients, and caregivers—in addition to industry and other stakeholders we communicate extensively with, have a clear window into our findings.

It’s our goal that you better understand our mission, as well as the utmost vigilance and care we apply in ensuring manufacturers are fully adhering to the medical product regulations designed to keep our medical supply one of the safest in the world.

Current Good Manufacturing Practices: An Area Seeing Consistent Violations

Current Good Manufacturing Practice (CGMP) regulations are a set of regulations and standards developed by the FDA to ensure the safety and quality of products, like food, pharmaceuticals, and medical devices. The minimum requirements for the methods, facilities, and controls used in the manufacturing, processing, and packing of a product, these regulations make sure that a product meets the intended quality standards and is safe for use.

However, far too often, our investigators working inside drug and other facilities uncover not just one, but multiple CGMP issues when conducting their inspections.

In fact, over the past 10 years, the top five observations consistently made by our investigators involve CGMP violations. These include failing to establish, maintain, and follow manufacturing standard operating procedures (or SOPs); missing scientifically sound laboratory procedures; and neglecting to investigate discrepancies or product failures when they occur.

These violations are important to pay attention to as they can be an indication that the manufacturer may not be able to consistently meet the safety and quality standards of the medical products they manufacture.

Let’s look at drug inspections. We compiled our observational findings from drug facility inspections over the past 10 years, breaking that data down into three categories: all inspections, domestic inspections, and foreign inspections. We also looked at inspections conducted at compounding facilities under relevant sections (503A and 503B) of the Federal Food, Drug, and Cosmetic Act.

Regardless of the way we classified the data, the same top five inspection observations prevailed:

Top Five Drug Inspection Observations Over the Past Decade

Drug inspection observations (This covers all inspection types, both domestic and foreign.)	Procedures not in writing or fully followed Product discrepancies and/or failures were not investigated Lack of scientifically sound laboratory controls Absence of written procedures Cleaning, sanitizing, or maintenance discrepancies
Domestic drug inspection observations	Procedures not in writing or fully followed Investigations of discrepancies or failures lacking Absence of scientifically sound laboratory controls Absence of written procedures Cleaning, sanitizing, or maintenance discrepancies
Foreign drug inspection observations	Procedures not in writing or fully followed Absence of scientifically sound laboratory controls Investigations of discrepancies or failures lacking Absence of written procedures Insufficient procedures for sterile drug products

Ensuring manufacturers compliance with CGMP is just one piece of an FDA inspection. Our specially trained and knowledge-equipped drug and medical product investigators also assess a firm’s quality system. With regards to drug inspections, and in light of the data above, our investigators also look closely at the manufacturer’s pharmaceutical quality system, or PQS, while conducting their on-site inspections.

A robust, comprehensive PQS assures the following: that the desired product quality is routinely met, suitable process performance is achieved, the set of controls are appropriate, improvement opportunities are identified and evaluated, and the body of knowledge is continually expanded. A manufacturer’s PQS is critical to ensuring drug products are manufactured to meet the desired quality and performance attributes—with every batch that comes off the manufacturing line.

Minimizes Risk of Shortages Too

A robust quality program should not only result in fewer quality issues—thus minimizing the risk of product recalls—but it also reduces the chances of product shortages. When quality issues arise in manufacturing facilities, recalls and/or plant shutdowns may necessarily follow, having a direct impact on the supply of a given product.

This can have serious, if not devastating, consequences for patients with a critical need for medical products.

Vaccines, Medical Devices, and Other Products

Our investigators observe some of the same issues with other medical products, including biological products—such as vaccines, blood, and gene therapies—and medical devices. The following table highlights our data over the past 10 years for all biologics and device inspections, observations which have remained consistent year after year.

Top Five Biological Product and Medical Device Inspection Observations Over the Past Decade

Biologics inspection observations	Lack of, or inadequate, standard operating procedures Thorough investigations lacking Concurrent documentation lacking Lack of, or inadequate, required records Biological product deviation report missing or inadequate
Devices inspection observations	Lack of, or inadequate, procedures Lack of, or inadequate, complaint procedures Purchasing controls, or lack of, or inadequate, procedures Lack of written medical device reporting procedures Lack of, or inadequate, process validation

We continue to strongly urge manufacturers to take a comprehensive look at their quality systems and make sure they have updated processes and procedures in place to handle complaints and adverse events reported by patients. It’s vital that manufacturers are prepared to conduct thorough investigations when receiving such critical feedback.

Continual Improvement and a Culture of Quality

The issues identified by our investigators also underscore the need for continual improvement in medical product manufacturing.

Compliance with FDA regulations is a minimal standard for responsible manufacturers. Manufacturers should also demonstrate a commitment to quality that reflects a diligence towards continuous improvement as well. When manufacturers have a commitment to continual improvements, patients have more reliable access to high-quality drugs and other medical products.

Companies spend years researching and reviewing products to help ensure every medical product sold is safe and performs as described. Yet, poor quality systems compromise those significant investments and safeguards. It’s simply a fact that manufacturers with a strong quality culture, and a robust PQS emphasizing continuous improvements, have far fewer issues.

While the FDA and OII play a vital role in ensuring Americans and their families have quality medical products in this country, it is the shared responsibility of all manufacturers to leverage innovation in their quest to making medical products of the highest and most reliable quality.

When it comes to patient safety, there is simply no room for error.