By Kenneth Christie, COO, VTS Consultants, Inc.
In the TV series Fear Factor, contestants had to overcome various challenges that most of us found disgusting and/or frightening in order to win a large cash prize. If they failed, their hopes were gone and the contest ended for them. The same can be true for the pharmaceutical industry in trying to achieve the “prize” of being found compliant when audited. While the challenges faced by the TV contestants were obvious, the fear factors industry faces are several, and the impact of each is significant. As a disclaimer, these fear factors are not published in any year-end regulatory summary, but rather are based on my experience working with companies ranging from startups to Big Pharma — as each strives to claim their compliance with applicable regulations. The top three fear factors of industry, as demonstrated by their actions, are summarized below.
1. I don’t understand the applicable regulatory requirements.
While it may be a surprise to many, it has become apparent, through years of auditing suppliers, drug and API manufacturers, and others, that the first fear factor encountered is a lack of understanding of the regulatory or industry requirements applicable to the product or service provided. In addition, many audit findings applicable to suppliers uncovered the fact that they were unaware of the regulations against which their customers audited them. It is essential that suppliers realize the nature of the industry they provide their product or service to and what they need to have in place to be compliant with their customers’ expectations. Because most suppliers are not audited by the FDA, the final responsibility lies with the customer. As a result, not only must the customer assure the suppler is compliant with the regulations that apply to them, such as ISO or CLIA in the case of laboratories, but that their processes also comply with the quality regulations that cover the customer’s product.
The most common shortcoming was often found in the area of documentation, notification of changes, and investigations of any complaints received. I do not mean to imply these observations apply to many companies, but when found they have a significant impact on the results for both parties. To avoid this factor, quality agreements need to spell out the expectations of both parties so there are no surprises when an audit is performed. The FDA has just published its current Guidance to Industry titled Contract Manufacturing Arrangements for Drugs: Quality Agreements (November 2016), which defines the importance of such agreements to help assure compliance with cGMPs. If companies have a supplier qualification program, shortcomings should be noted when performing an on-site audit to evaluate the acceptability of the supplier’s quality systems. As with the other fear factors to follow, proper and adequate vetting of potential critical suppliers will certainly help avoid these concerns.
The same is true for drug manufacturers and the level of ignorance displayed by some when entering the sterile product market. In cases like this, their level of understanding tends to remain with the nature of their current non-sterile product and wrongly assume there “isn’t much difference between the two.” This couldn’t be further from the truth. For instance, one of the biggest differences in terms of compliance is the requirement for operators and routine personnel to understand the aseptic techniques and environmental monitoring required to assure the sterility assurance of the product.
Not only do companies need to know the applicable U.S. regulations but also those of foreign countries, should the product be sold overseas. In many cases, the assumed time line to become compliant is another sign of the lack of understanding by management of the requirements. The typical approach is to do it quickly, within an unrealistic budget, and make sure the desired date is met. This is certainly not the norm, but to think this scenario doesn’t exist is also a misconception. I have even been exposed to an attitude that can only be described as “the longer we don’t talk about it, the better our chances it will go away.”
Of the three fear factors I discuss in this article, this is probably the easiest to address. It starts with management that is committed to achieving compliance, a strong quality system staffed by knowledgeable people, and a workforce that is trained on the regulations. In my experience, the best-run companies are those that have upper management with production experience and a commitment to doing things right. Having the manufacturing experience provides a more realistic approach that includes prompt resolution of deviations and better identification of probable cause and corrective actions. At the same time, there is no hesitation to quarantine product when things go awry, despite the pressure to send product out the door. Companies that have this structure are better able to perform a risk assessment of their processes, set priorities based on the levels of risk defined, and continually work on achievement and maintenance of their degree of compliance.
2. I don’t have sufficient resources to support the quality system.
The second fear factor is the availability of resources to perform the responsibilities of the quality unit. As supply chains grow and outsourcing of activities increases, there is a growing need to assure that these providers are managed, and that there is assurance that items purchased or services provided meet the expectations of the company. As the activities normally performed at the company are outsourced, there tends to be a reduction in the workforce (often in the quality unit), until shortcomings are discovered during an audit. Then the pendulum swings 180 degrees and the quality unit once again swells to a point where efficiency is lost. It seems like the mindset is the larger the quality unit, the better our chances to be compliant. There seems to be little attempt to evaluate whether the problem was truly too few resources or lack of management of the workloads of those already employed. (Please note, I certainly respect anyone in quality based on the vast array of responsibilities associated with all quality positions.)
The issue of resources is most demanding today, as companies strive to minimize overall costs and increase their margins on the products or services they provide, while still trying to establish an acceptable level of compliance. By running lean, companies are continually increasing the outsourcing of many activities normally done in house. This can include cleaning, laboratory testing, packaging and labeling, calibrations, and facility and equipment qualifications, to name a few. There is nothing wrong with this practice, but companies must not forget that they are the ones responsible for the management of these activities — not the contracted service providers. Companies must be aware of problems that occur, be an active part of their resolution, and both approve and understand the processes performed. I have experience with many companies that contracted out qualification services and made no attempt to understand what was done, how, or why. Because of this, I would often wonder how any question raised during an audit could be addressed, as no one was involved with the testing or even tried to learn.
3. Compliance-related costs are greater than I can afford.
The third factor — and one that should not surprise anyone — is cost. Today, the bottom line tends to dictate the degree of compliance, the management of the quality system, and the growing expectations put on staff and consultants, both of which are impacted by the first two factors described above. It is understood by all of us that the “business” of business is to make money to pay salaries and benefits and to expand, but when the expenditures are cut or minimized in areas critical to achieving and maintaining compliance, the problems only start to multiply and grow. The final results in many cases are warning letters or even consent decrees whose financial impact far exceed what it would have cost to do things right from the start.
There will always be the need for the industry to strike a balance between the cost of compliance and the economic status of the company. What cannot happen is putting the public at risk at the expense of forgoing compliance due to cost. The notion that the companies that have the deepest pockets are the best and most compliant is also not completely true. Look at the size of the companies that have entered into consent decrees over the years, and you will find some of the largest and most well-known of today’s pharmaceutical giants. We all have heard of the saying that quality needs to be built into the process to achieve quality results. By doing so, the costs associated with compliance will drop over time as deviations are reduced, processes are streamlined, and business and opportunities increase due to fewer regulatory issues.
In summary, compliance does not come cheap; it demands maintenance of the processes employed and training that will always be required as regulations change with time. By overcoming the fears listed above, the prize is there to those who do it the best.
About The Author:
Ken Christie has over 30 years of sterile manufacturing and regulatory GMP consulting experience in the areas of quality assurance and validation management in the pharmaceutical and biotechnology industries. He is currently the COO for VTS Consultants, Inc., where his responsibilities include quality system auditing, GMP training, and serving as a subject matter expert for aseptic manufacturing processes, equipment and utilities, medical devices, and solid dosage processes on a global basis. Mr. Christie also performs vendor audits, conducts site pre-approval inspections, and assists clients with addressing and correcting regulatory observations.
Mr. Christie is a speaker and trainer for several professional organizations and is a published author of several articles dealing with the challenges of aseptic processing. He has served as a member of the ISPE’s Professional Certification Commission (PCC) as an Examination Development Committee (EDC) member. Mr. Christie earned a B.S. in biology from Shippensburg State University (PA) and an executive MBA from Michigan State University. You can connect with him on LinkedIn or contact him at email@example.com or 413-253-0077.