It is alarming to see prominent pharmaceutical industry names in the headlines these days regarding manufacturing issues serious enough to require recalls and plant closings, and for the DOJ to be compelled to seek prosecution. Is it just a matter of the FDA increasing their surveillance scrutiny and compliance enforcement or is there really something more fundamental going on with pharmaceutical manufacturing?
Even with all the automation, IT support, instrumentation, purpose built facilities, and technical expertise, pharmaceutical manufacturing is difficult. Those who do or have done pharmaceutical manufacturing know how challenging it is to maintain consistency and the high quality of products, batch after batch for tens of millions of tablets, capsules, or doses, year in and year out.
Pharmaceutical manufacturing is tightly regulated for quality with highly developed quality systems supported by rigorously defined product specifications, detailed SOPs (standard operating procedures), training requirements, job qualification expectations, and mandatory supervisory and quality assurance (QA) checks and balances. One of the biggest question I had when these issues started to more frequently hit the press was, “where was Quality Assurance management?”
I believe with all the regulatory safeguards supposedly built into pharmaceutical manufacturing, industry executives who have never worked in manufacturing have very simplistic views of manufacturing, have developed a false sense of security about compliance requirements, and many are probably taking quality of manufacturing for granted.
Here are a few issues, attitudes, and situations that may be at the root of some of these pharmaceutical manufacturing issues. Many if not all of them have to do with management’s perspective or the perspectives and expectations they project to their manufacturing teams.
- Management thinking that manufacturing is all about efficiency, so “let’s have manufacturing find another 5% reduction in cost of production.” If you make this request year after year, at what point do you compromise quality?
- With the jobs so well defined in our SOPs, “we can train anybody to do these jobs. How hard can it be?”
- Once the process is defined, it’s just a matter of production execution and efficiency
- Repetitive, routine operational steps by otherwise competent operators can lead to complacency, including at the checking and double checking steps of the supervisory role
- we don’t need QA people who are going to be difficult to work with (interpretation…we don’t need people who aren’t flexible in their process reviews and sign-offs)
- “we are not making any product when we are cleaning.” “what is the longest stretch of time between cleanings that we can justify?” Facility, manufacturing room, and equipment cleaning time, when viewed as non-production time (reduces productivity), puts pressure on performance metrics.
- Similarly, “when people are training they are not making product”
- “We are not going to let a meticulous operator get in the way of making our numbers. Find a new operator.”
- “I am so busy with paperwork…nobody is going to know if I just sign off on this, even though I haven’t really checked it”
- “Nobody in management needs to know, we’ll just write that batch off as waste”
- “Let’s just do another sampling. I’m sure the batch will pass”
- “let’s just get a management authorized override for that deviation”
- We can’t afford the shutdown time to make the necessary upgrades to the process, even though it makes sense.
- FDA will require a new set of trials if we make these changes to our outdated process
- “We’ll never get caught up with these CAPAs” (Corrective Action and Preventive Action). Sometimes the hardest but most important never get addressed in a timely fashion despite SOP defined prioritizations and timelines that are supposed to safeguard against delaying the fixes.
OK. I think I have made my point. Time for pharmaceutical manufacturing to get some respect and more importantly, some much needed investment. I’m not talking just about buildings and machines although that may be in order for some. I’m talking about putting quality standards of production ahead of production output metrics (no game playing, not just lip service). I believe well managed manufacturing teams of competent, conscientious operators, supervisors, and QA/QC staff with expertise and integrity will take pride in delivering high quality products as efficiently as they feel is possible. It is the “well managed” part that I believe may be missing in some manufacturing operations.
It is also time for pharmaceutical company executives to appreciate the contribution manufacturing makes to the revenue line and not just look at the expense line impact. Some executives, unfortunately, now know the negative impact manufacturing can have on revenues, especially if you take it for granted and don’t pay attention to it.