The fields of regulatory science and quality management are constantly changing as industry needs shift and new regulations are enacted to ensure product safety. As new technologies and therapeutic options emerge and market demand for new products grows – think CBD in all its permutations – compliance will become even more closely monitored as regulators strive to keep consumers safe from improperly manufactured products with inaccurate performance claims.
That means that 2020 will be a busy year for regulators. The FDA was largely in flux throughout 2019 as it transitioned from Commissioner to Acting to Commissioner but is now expected to pay more attention to novel and existing devices, drugs and biologics. There are still some questions as to the FDA’s direction on CBD and exactly what leaders and manufacturers in regulated industries should expect from the agency, but indications are that it will be more vigilant about enforcing compliance. This could result in the distribution of more Form 483s and warning letters to manufacturers and perhaps more severe enforcement actions.
Here is a brief summary of compliance trends from 2019, and where compliance and quality are expected to be focus on for 2020.
What to Expect from FDA Inspections
Inspections are both a manufacturer’s worst nightmare and the FDA’s preferred method of gathering data on how companies are maintaining their quality and compliance programs. In most industries – save medical devices and overseas facilities – inspections are carried out without notice in order to provide inspectors a real-world glimpse into how well companies adhere to regulatory and quality requirements every day and not just when they know inspectors are coming.
While FDA inspections are best known for identifying compliance gaps, they can also provide manufacturers an opportunity to establish a relationship with inspectors and the agency. Over time, it is possible to lay the foundation for a strong working relationship with the FDA, which can streamline inspections and enable the manufacturer to maintain compliance and avoid enforcement actions.
The FDA conducted over 18,000 inspections in 2019, and the agency is expected to conduct more in 2020 and years to come. Here are some key areas of FDA focus to bear in mind when preparing for an inspection:
Documentation of thorough internal investigations
Manufacturers should prioritize documentation and timely closure of Corrective and Preventive Action (CAPA) reports to document product problems and deviations from established process.
Adverse event reporting
The FDA has been known to react quickly and forcefully when adverse event information is withheld, as this data helps them identify risks to patient and consumer health. A thorough reporting system will demonstrate compliance and set the tone for a cordial inspection.
Adequate staff training
Untrained staff will not be able to appropriately answer inspector questions and may prove a hindrance in achieving a vigorous and effective quality system, so staff should receive enough documented training to support the quality plan.
Response to inspection observations
Citations will happen, but what the FDA really wants to see is a prompt and comprehensive response, so quality teams should prioritize the documentation and plan to address noted deficiencies and prevent additional citations.
The most robust quality system will be meaningless if there is not enough staff to support it. The regulatory and quality department should have enough staff to meet the facility needs, and sufficient budget to outsource tasks as appropriate.
Trends in FDA Warning Letters
The past year saw a slight increase in the number of FDA warning letters issued (15,017) compared to 2018, with the overwhelming majority of letters distributed to tobacco companies. In 2019 the agency stepped up its investigations into Electronic Nicotine Delivery Systems – commonly known as vaping devices – specifically in response to spikes in diagnoses of serious lung disease among users and manufacturer’s marketing activities aimed directly at children and teenagers.
A drastic increase in the demand for CBD oil products brought increased scrutiny to manufacturers as a result of unsubstantiated curative and therapeutic claims on CBD product labels. And drug and medical device manufacturers did not escape unscathed. 2019 saw the most warning letters issued to makers of finished products in recent history, and the number of inspection citations issued to OTC and prescription drug makers continued its upward trend in 2019.
Somewhat surprisingly, the most common deficiency noted in FDA warning letters is the lack of adherence to basic GMP and quality requirements. The agency is noting a dearth of written procedures and policies, and in some cases, a complete lack of a quality system or plan. This is notable because 21 CFR 211 plainly defines the requirements of a basic quality system, but FDA data seems to suggest that some manufacturers are viewing compliance as an optional expense and not a regulatory requirement
Quality Challenges for 2020 and Beyond
The top three challenges facing quality and regulatory managers in the coming year are maintaining compliance, improving production processes and product performance, and budgets and resources. The increase in FDA warning letters that cite deficiencies in basic quality standards indicates just how important it is for manufacturers to place an emphasis on compliance, but that message may still not generate the attention that regulatory compliance requires. A well-defined and sufficiently staffed quality plan can help companies avoid these GMP standards most often cited by FDA inspectors:
- Definition of the responsibilities of the quality unit
- Availability of written procedures
- Testing and release plans for distribution
- Production record review
- Stability testing and approval or rejection of components, drugs product containers, and closures
For device makers, the same requirements apply but the list of common deficiencies is slightly different, so manufacturers looking to stay compliant should focus on these key components of their quality plan:
- Thorough CAPA process
- Definitive product design controls
- Purchasing controls
- Process validation plan
- Documented product complaint files
As we head into the remainder of the new year, quality and compliance will continue to dominate regulated industries, and manufacturers who put a premium on developing a robust quality and compliance management system will be able to more quickly identify and address issues before they can impact production and catch the eye of an FDA inspector. The establishment of performance-driven metrics for quality and compliance can help executives demonstrate the value of an established quality management system and the positive impact compliance can have on a product’s launch timeline and the organization’s bottom line.