By James Morris, executive director, Pharmaceutical Services, NSF International
We like simplicity. Yet in pharmaceutical operations we have become very good at making things more complex than they need to be. Overcomplicating things in pharma operations can take many different forms. This article illustrates a few areas where companies tend to make matters worse and highlights areas where both industry and regulatory agency leaders should push back and focus on simplification.
1. Organizational Complexity
In plant operations we have heads of manufacturing, heads of quality, heads of engineering, etc. More recently, companies are adding a head of data integrity. Rather than embedding the right behaviors related to data integrity into each department, some companies have chosen to add additional overhead by carving out a role for someone to oversee data integrity governance. Governance is needed, but must it result in additional headcount? Any time we add additional personnel in an oversight function such as data integrity governance or quality assurance (QA), we risk adding complexity at the shop floor level. We need to push against this tendency.
2. Quality Systems Complexity
Our quality systems need to be designed to ensure the right decisions are made regarding patient safety. Some sites, however, have an inordinate number of open investigations and corrective and preventive actions (CAPAs). Over time, the backlog becomes insurmountable. The underlying reasons for this situation vary, but it often comes down to ineffective triage of quality events and a lack of ownership of deviation closure at the unit operation level. If the backlog approaches 10 percent of the total number of investigations managed in a year, then something is intrinsically wrong with the system. Managing the system to ensure smooth flow requires system simplicity and organizational focus. It’s not easy, but it’s much easier than explaining why a simple investigation took over 60 days to close.
3. Procedural Complexity
The level of procedural noncompliance at many manufacturing sites exceeds 30 percent. This can be assessed very easily. Randomly select 10 standard operating procedures (SOPs) from various departments, and it would be fortunate if you find seven out of 10 SOPs actually being followed as written. This does not necessarily mean that unit operations are negligent in their duties or putting patients at risk. Remember, batch manufacturing and control records are developed to guide operating personnel and ensure that validated methods are meticulously followed. Procedural noncompliance, however, points to another fundamental weakness that companies must guard against regularly.
What Is The Path Forward?
Senior management needs to recognize the importance of reducing complexity at all three levels. Some companies have created a gatekeeper function whose role is to push back and guard against procedural complexity. Once again, we are overcomplicating things by charging a department with an oversight function.
Overhead related to QA and other oversight functions must be dramatically reduced. I used to be suspicious of a company whose quality unit represented less than 15 to 20 percent of the operational headcount at a plant site. I now am suspicious of any operation whose quality function represents more than 15 to 20 percent of the operational headcount at a plant site.
System complexity must be driven down by developing methods designed to triage events and ensure a risk-based approach is followed. This is so that investigations of events that represent the greatest patient, compliance, or business risks are given the most attention. Events that present less risk must still be managed, but managed quickly within the unit operation. A site that creates an investigations unit or hires teams of outside contractors to manage an investigation backlog should undertake a careful review of their underlying system and the maturity of their quality unit.
Procedural complexity can be tackled by following best practices such as the use of diagrams, bulleted text, flow charts, etc. Applying the principles of cognitive load reduction in document and form design is also an option. These SOP design changes, however, only offer incremental improvements. Once again, more significant action is recommended. If your site currently manages 750 SOPs and 100 work instructions, I recommend flipping this ratio and moving to 100 SOPs and 750 or even 1,000 work instructions. Work instructions are simple, readily accessible, task-oriented instructions designed with the user in mind. More and more companies are moving in this direction, and it makes sense. These companies keep the user (plant operator, supervisor, lab technician) in mind, strive to reduce cognitive load, and ensure information is presented in chunks and repeated until the right habits are formed.
The path to move away from over complexity is also greatly influenced by the good manufacturing practice (GMP) auditor. An auditor will often raise findings that have questionable merit and result in the auditee reacting by adding complexity to their procedures. Contract manufacturing organizations regularly complain that their SOPs become a patchwork of stakeholder expectations, to the point that the SOPs become difficult to follow. We need to push against this tendency as well.
Ultimately, regulatory agencies have significant influence over the complexity of pharmaceutical operations. A regulatory audit finding carries enormous weight, as no company wishes to risk regulatory action by the FDA or another agency. Ranking inspection findings as done by EMA in critical, major, and other categories would help companies calibrate their responses. Regulatory inspectors who evaluate the health of companies’ quality systems (e.g., number of open CAPAs, open change controls) shift the emphasis inside companies and encourage quality system simplification, so long as the regulatory inspector does not also expect low-risk issues to warrant extensive documented evidence on the company side. In fact, the development of regulatory guidance should frankly be measured by whether the guidance is clear and well structured. Recent FDA guidance on data integrity appears to increase batch release expectations, requiring audit trail reviews with each batch. Interpretations as to what this means will vary, and auditors risk citing companies for GMP noncompliance unnecessarily. All stakeholders involved in pharmaceutical product supply must guard against the ratcheting up of GMP expectations and the implementation of unclear guidance.
As we know, simplifying is extremely hard but incredibly valuable. Keeping the above-mentioned principles in mind will help you lead your unit and your site to a more reliable, less stressful place from an operational point of view. And a pragmatic approach to regulatory inspection findings will help companies apply their resources to where they matter most in manufacturing – on the shop floor.
About The Author:
Jim Morris has over 25 years of pharmaceutical management experience in both plant operations and corporate offices in the U.S. and Europe. He has held positions as deputy director of QA/QC and regulatory affairs at Mass Biologics, director of QA/QC for the Biologics business unit of Cilag AG, and a number of quality assurance and manufacturing roles with Pfizer over a 16-year timeframe, culminating as the head of quality assurance in Latina, Italy. His areas of recognized expertise include: quality leadership development, supply chain auditing and managing audit programs; quality management systems; parenteral product manufacture and compliance; and OTC product manufacture and compliance.