In recent years, there has been an increased focus on ensuring that drug facilities like pharmaceutical and biotech companies adhere to regulations and manufacturing standards. As a result, federal agencies like the U.S. Food and Drug Administration (FDA) have ramped up inspections and audits of these facilities to ensure compliance and patient safety.
Most Common Violations
When reviewing the data from recent FDA audits and inspections, there are a few violations that come up again and again as the most frequently cited issues:
- Procedures and Protocols Not Followed or Documented
- Quality Control Issues
- Facility and Equipment Concerns
- Staff Training Deficiencies
Let’s take a closer look at each of these common violations.
Procedures and Protocols Not Followed or Documented
One of the most common violations noted during audits is a failure to follow or properly document standard operating procedures and protocols. This includes things like:
- Not following written procedures for performing critical processes like equipment cleaning and maintenance, quality checks, etc.
- Failing to document quality control checks, equipment calibration, staff training, etc.
- Deviating from standard operating procedures without justification or approval
- Missing or incomplete batch records and documentation
Having detailed written procedures and protocols is useless if they are not being adhered to consistently. Likewise, simply performing critical tasks like equipment maintenance is not enough – facilities must also diligently document these activities. When auditors find issues in either actually following procedures or documenting protocol adherence, it is sure to result in a violation citation.
Quality Control Issues
While related to documentation and procedural issues, quality control problems are significant enough to warrant their own discussion. Some examples of frequently cited QC violations include:
- Failing to thoroughly investigate quality control failures like OOS (out-of-specification) test results
- Releasing batches that failed quality control testing
- Failing to conduct quality control testing at required intervals
- Not adhering to established specifications and acceptance criteria
- Releasing products without final quality approval
In an environment like pharmaceutical manufacturing, quality cannot be sacrificed or overlooked. When auditors find issues with a facility’s quality control processes, it undermines confidence in the safety and integrity of the entire operation.
Facility and Equipment Concerns
To produce quality drug products, facilities must be designed and maintained in a way that minimizes risks of contamination and error. However, FDA inspections often uncover deficiencies in:
- Facility design and work flow – issues like overcrowding, insufficient light, poorly marked areas, etc.
- Sanitation and maintenance – equipment, fixtures, and work areas that are dirty, cluttered, or in disrepair
- Environmental monitoring – failing to adequately monitor things like air particles, microbiologics, and humidity
- Calibration and maintenance of equipment – skipping required calibrations or performance verifications
When the physical plant and equipment are not up to standards, it calls into question the safety and quality of the products being made there. These types of violations seem obvious, but they continue to be routinely cited by inspectors.
Staff Training Deficiencies
The people working within a pharmaceutical facility are just as important as the facility and equipment itself. However, many firms fail to adequately train personnel, leading to violations like:
- Inadequate employee training on performing assigned duties and following procedures
- Failing to provide training on new processes and equipment before implementation
- Not providing ongoing and refresher training at appropriate intervals
- Inability of staff to demonstrate proficiency and knowledge of procedures
- Lack of documented training records and qualifications
Employees must have the proper knowledge and skills to perform their jobs accurately and compliantly. Failing to provide adequate training leaves staff prone to errors and puts quality at risk.
Underlying Causes
While these violations may seem straightforward on the surface, there are often deeper reasons why drug facilities continue to receive citations for the same issues over and over. Some potential root causes include:
- Lack of focus on quality culture – Quality is not ingrained as a top priority across all levels of the organization.
- Poor change management – New processes, equipment, staff, etc. are not properly validated and integrated into the existing systems.
- Ineffective quality assurance – QA does not have the resources or authority to ensure procedures and standards are adhered to.
- Complacency – When not faced with consequences, facilities get lax about continued compliance.
- Communication breakdowns – Violations occur when information does not get shared properly across departments.
- High turnover – Loss of knowledgeable personnel leads to loss of “institutional knowledge” and continuity.
- Lack of resources – Personnel shortages, budget constraints, and inadequate systems can impede compliance.
Rather than looking at each violation in isolation, firms need to trace violations back to their root cause(s) in order to develop holistic and sustainable corrective actions.
Steps to Reduce Violations
Drug manufacturing facilities that get caught in a cycle of repeat violations from audit to audit may benefit from taking proactive steps like:
- Conduct internal audits – Don’t just rely on outside inspectors to catch issues; perform regular internal audits to identify gaps proactively.
- Increase training – Look for opportunities to train staff beyond mandatory requirements to reinforce skills and knowledge.
- Enhance documentation – Continuously improve document management and record keeping practices.
- Review procedures frequently – Keep SOPs current by reviewing at least annually.
- Close the loop on corrective actions – Don’t just file and forget CAPA reports; verify that proposed fixes are implemented and effective.
- Prioritize quality culture – Senior management must consistently emphasize that quality comes before productivity and cost.
- Welcome auditors – See inspectors as an opportunity to improve rather than a threat to be feared.
Staying ahead of common violations takes work, but doing so reduces compliance risks and protects patient safety. For companies repeatedly cited for similar violations, the effort to implement systemic improvements is well worth it.
Conclusion
In summary, audits and inspections of pharmaceutical and biotech facilities frequently uncover issues in procedural compliance, quality control, facilities and equipment, and personnel training. Addressing these rampant violations requires moving beyond viewing them simply as isolated incidents. Companies must dig deeper to reveal the underlying gaps and vulnerabilities in their quality system and culture. Proactively closing these gaps through more rigorous training, documentation, and internal controls can break the cycle of repeat violations.