As a consultant, I am often brought in to assess systems, perform gap analyses or to audit. In many respects it is the same activity. I look at what is in place in the form of documents (SOPs and policies) and in processes in action in their operations. Some of these clients are large pharma or biopharma but a large number are relatively new and small operations with much of their activities outsourced to third parties.

Now let me stress, as a consultant, I am totally against getting consultants to write SOPs. It is not because I can not write an SOP. It is because a document that is written must be owned by the eventual company and to get ownership requires, in my mind, an active involvement in the production of the document and process. Ordinarily, I will supply key elements I would expect to see in a document or process. I will review the document to modify it to include elements forgotten or to restructure for clarity.

My approach is the same for both type of clients when I come in to assess. I use the classic moniker of “say what you do, do what you say, prove it, improve it” or putting it simply, documents, execution, records, improvements. So what do I see? In large companies, I often see well established elements with often strengths and weaknesses. So my tasks are relatively straightforward. But in small companies do I see the same? The simple answer is No.

What I see is groups of people working furiously to keep momentum going. This results in major gaps in systems. Many times, procedures are not in place and even if they are, they do not reflect the process in place. Particularly when procedures are in place they are written vaguely with no clarity as to process. When you interview people to gain clarity, you find their processes as verbally described are often quite robust. But it is just not described in any formal document. But since the company is small everybody knows everybody else and communication is very much ad hoc. While this may work initially, as the companies grow they lose that advantage.

So what we have to do is get them to think through the actual processes, write them down and immortalize them in policies and SOPs. This is easier said than done. They are so busy, they do not have the time to get it down on paper. On many occasions, to get them to a better state, I take on the task of writing it down, then getting them to check for accuracy and then shepherd the documents through the system. Ordinarily, I am not a supporter of getting a consultant to write an SOP for the company. Even if written very well, there is no ownership within the organization. But this is different. You are not inventing a new process to implement, it is writing down what is actually done. Or at least that is how I justify going against my own philosophy.

My goal is to put into place procedures describing what is actually done in the company, in a manner that if all the employees disappear overnight, to be replaced in the morning with new people, there is a good chance the processes would be executed similarly as before. In other word a robust sustainable process. This is the first step in building a rugged Quality Management System.

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In the first article dealing with our surveys, we concluded that not all of the guidances issued had been implemented completely.  Even when they had been implemented, the implementation did not take advantage of all the potential.  For instance many companies were reluctant to  not work on certain technical areas even though their risk analysis indicated that these same areas were relatively unimportant and had little impact on product quality and patient outcome.  And why was that?  Perhaps they did not believe their analysis.  Perhaps they were afraid of inspectors disagreeing.

The second article (Part 2 of the survey) showed that even though guidances had been implemented, the impact on some of the most troublesome elements of the QMS was not as effective as hoped.  Some if you find your company not gaining as much traction as hoped, you are not alone in struggling to become more effective.

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I just had an article describing the Compounding industry and what the FDA is doing about it. Here is the link.

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Do you have deviations that just won’t go away?  Do they disappear for a couple of months only to reappear a few months later stronger than ever?  Have you ever wondered why?

I won’t try to say that there is one cause for this but one that I have found continuously is Human Error as a major cause of the problem.  The obvious CAPA for this observation is to retrain the operator and rewrite the SOP.  I have seen it often in companies.

When I go in to audit the QMS, this is one area I look for first.  I look at the CAPAs and tally up the retrain operator and the rewrite SOP ones and if I find it happens more than 10% of the time, I know where to focus.  Investigations are not thorough or in depth.

On a recent visit to a client, they had just exited from a grueling inspection by an agency with a total of 53 observations.  They had developed their responses which are really CAPAs in any other language.  There were a total of 135 CAPAs and 55% were “retrain operator” or “rewrite SOP”.  I asked the person in charge of getting the responses back and asked whether he thought it would correct the problem.  His reply was an honest “No, many of these problems we’ve seen before and tried that and it never works”.  So, I ask him why are you doing it again, remembering Einstein’s quote “insanity is doing the same thing again and expecting a different result”.  At least I think it’s Einstein.

I then asked, “Why did you do this when you know it will not work?”  The answer was a chilling “because the regulators will accept it and it will allow me to get back to making product!”  I wanted to say “Yes, in the same broken way as before”.

After talking with other people at the plant it became clear that their investigation skills and tools were deficient.  They could get to the human error point.  They recognized that somebody had made an error but they lacked the tools to investigate further as to why it occurred.  Was it a system that was defective, were the operators overloaded with work, were the work stations organized appropriately?

Very rarely is Human Error the root cause but rather Human Error is the symptom of things not functioning properly. It is often the result of a deficiency elsewhere.  No other industry accepts human error just our pharmaceutical one.

There are four main ways that that things fail and manifest as human errors. There has been plenty of research in this area but not in pharmaceuticals.

1. Culture – the culture allowing or encouraging people to not follow procedures. Initially it may be innocent. “I know the procedure is wrong, but we cannot change it”. “I know it says that, but this short cut will get you there quicker and we have a goal to get on the shift” – implying doing it by the rules won’t let you get there on time. This often occurs in cultures that are volume driven. “Get the product out the door at all costs”. One company even had a goal of “Speed over perfection”. That was a difficult one to puzzle out.
2. Systems – the systems in place just don’t work. The poor operator just can’t get it to work based on the equipment, layout, QMS in place. This can be a change control process that is no longer serving the plant, a deviation process that everybody avoids, a CAPA process that is viewed as a encumbrance. The systems are viewed as punishment. Gone has the goal that the systems are tools to help you stay on top of your processes. The goal of everybody is to move the paper to the next person as quickly as possible. These systems are often put in place at the Corporate level or by management without asking the practitioners how it should be done. The same occurs in lay out of equipment and processes. They are not designed with the user in mind but often by a corporate engineer in central headquarters. Often operators have to take readings, remember them and go to the other end of the room or even next door to log the data into the permanent record.  This also breeds scrap paper use for data transcription.
3. Procedures – this is where the procedures, batch records are wrong. It is often because they were not written by users but rather other bodies.                                                                                                            In one case I came across batch records being filled out and there appeared to be lots of   extraneous comments.     I asked about them and queried why.  “The batch records are wrong” was the response.  “Why don’t you change them?” I questioned.  “We can’t. We are not allowed to “ was the answer.  “Why can’t you?”, I asked. “Because Process Science owns them. They write them for us”  “If they write them, do they have the same equipment as you operating at a similar scale”.  “No”.     No wonder they are wrong. Nobody consulted the actual people operating the equipment.
4. People – which brings us to the people. They make mistakes for many reasons. The reasons are many and varied. It could be that the training was inadequate. Yes they know what to do but not why. They do not understand the criticality of the key steps. They don’t know why it must be done this way. They are rushed and in the rush they revert to the old way.

As you read through the examples above, you will see a lot of similarity and overlap and that is because, it is rarely only one of the above that fails.  It actually starts at the management level with culture.  They set the tone that creates the systems, procedures and people to fail.

So how can you detect that you have a culture problem?  A systems problem?  Poor procedures? Or people prone to human errors?

You know you have problem or potentially one if you can say yes to any of the following:

Culture Problems include

• Silos with poor communication between
• Box checking mentality
• Firefighting all day and everyday
• Deadlines that are never met
• Deviations are considered bad and people are punished
• A blame culture that never learns from mistakes
• People unwilling to raise the alarm for fear of punishment
• Heavy reliance on final check – QA will catch it
• Metrics that drive the wrong behaviour

System problems are evident by these

• Congestion on the plant floor
• Poor work flows
• Physical conditions not adequate – lighting, temperature, humidity
• Unreliable equipment that breaks down
• Poor ergonomics of operators
• Electronic systems that are no longer tools serving the worker
• People avoiding using e-systems
• Don’t know the cost of non-conformance
• User not involved in design

Procedure problems are exemplified by

• Long complex SOPs – they read like War and Peace
• Too many double or even triple checks
• SOPs written to satisfy auditors or regulators not for operators
• CAPAs never working
• All investigations / CAPAs must be complete in 30 days
• Everything given equal importance

Which brings us to People

• No time for breaks
• Workers operating on permanent overtime
• Multitasking that does not work
• Reliance on memory because documents and records aren’t where the work is
• Training explains the how but not the why. No understanding of the consequences of the procedure
• Too many distractions
• Training in a class room versus where the job is done

Of course this is not a comprehensive list but you get the picture!!

To get rid of all these types of problem requires both management and workers to take responsibility.  We must move to a culture exemplified by

1. Create a positive attitude to human error. People make mistakes because the systems supporting them fail them. The error is pointing out an opportunity for improvement.
2. Create a blame free culture. We must have a freedom to speak out where we see an issue and focus on the event and not who did it. Ask the question “what went wrong?” rather than “what did you do wrong?”
3. Drive out complexity. Complexity is the enemy, it makes SOPs unworkable and an unworkable SOP translates to error. Reward simple procedures.
4. Use user centered design. Get the workers involved in writing SOP, Batch Records, designing equipment and process layout. You will create ownership and it will be right.
5. Introduce safeguards into processes, equipment. The operator knows what can go wrong, what they do under stress. Ask for their advice.
6. Have a rapid reporting system. A system that responds in hours, not days, week or never.
7. Seek out and remove risk. The workforce is your best friend to identify what or could go wrong. They see it every day.
8. Create education and not training programs. Education explains how and what but also why it is done this way. It includes what can go wrong if steps are done wrong. Tells you what the critical steps are and why the new is better than the old.
9. Management must assign roles and responsibilities and hold people accountable. Ownership and pride in the job well done ensues.

The road is a long one fraught with challenges but as my father used to wisely tell me “Knowing you have a problem is 50% of the way to solving it”.  How true!!!!

Posted in Commercial Manufacturing, GMP, inspections, News, Quality Management Systems, regulatory citations, Warning Letter| Tags: Services, SOPs|2 Comments

In the first quarter of 2014, 3 Indian companies were issued warning letter (see my posting on the blog) whereas 7 pharmacies were hit.  Statistically significant?  Perhaps.

After the debacle of the New England Compounding Center about a year ago, the FDA has been on a rampage in the Pharmacy world.  I am no lawyer but the way I read it is the pharmacies are using a loophole in the law centered around the  issues of FDA jurisdiction.  FDA basically regulates interstate distribution of drugs, so make a drug in state X and “export” it to state Y – yep FDA has jurisdiction. So the manufacturers of drugs are under FDA rule.

Now, pharmacies are allowed to take these drugs and dispense prescriptions.  So when you go to your corner pharmacist, you can see them dispensing.  Counting out pills and putting them into bottles.  Hardly much risk here so long as they don’t muddle them up, get them cross contaminated  etc.  But they can also do further dispensing.  For instance, they can take a sterile vial or bottle of a drug and dispense it to another sterile container.  Now this is another matter.  What we are describing is aseptic processing.  As we all know that’s a risky business.  How many manufacturers fall foul of the regulations in industry?  The number of warning letters are numerous.

But it seems that FDA can not step in unless there is a demonstrated safety calamity.  But we don’t want to wait for that each and every time.  So what can the FDA do?  Their tack is to inspect these operations when they suspect that the Pharmacy has overstepped their authority.  It seems that in a majority of the 7 letter this quarter they have seen that the pharmacies have been dispensing these aseptically prepared drugs without prescriptions and compounding several drugs together.  Some of these drugs have different regimes of taking the drug.  Ergo, they are no longer dispensing, but manufacturing.

Now when they go in and inspect they cite for lack of GMP adherences and the story goes on.  Call me naive, but if I go to a pharmacy, I want an assurance that the drugs I am receiving are not adulterated.  I don’t care who regulates them but I want it done properly.  Clearly the Boards of Pharmacy have not been doing a good job (they are the ones who regulate at a state level rather than FDA).  What we have here is a standard clash between Federal and state control – we see it every day in other matters but in this case they are using our health as a pawn in the game.

Keep up the good work FDA.

He is the link to the 7 warning letters

Nora Apothecary Services ,  Lowlite Investments DBA Olympia Pharmacy, Pallimed Solutions, Wedgewood Village Pharmacy, Total Pharmacy Services ,Avella of Deer Valley, Village Fertility Pharmacy

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