It’s been about 1 year since the FDA issued its Guidance on Contract Manufacturing. Based on what I read in blogs and social media like LinkedIn, I am sure not all companies are really up to speed. At an IBC conference recently, I presented a paper on the guidance and putting it into practice. It was so well received, I was asked to write an article on the topic by Bioprocessing International and here it is. Good reading!!
The Calcott Consulting Blog:
Articles on GMP:
One of the clients of a colleague of mine is undergoing a culture change in their operations from the “old-style” quality to a newer style. What do I mean by that? The old style is characterized by the Silo mentality, the us versus them, distrust, Quality that can be characterized as a Dr. No approach. I think you know what I mean. You may have worked at a company like that in your career. Actually you can see them and the results in warning letters posted by FDA if you have never experienced this before. Although all do not end up with warning letters. Many operate for years this way.
This will be a long journey involving a lot of small steps. It is not something that happens overnight.
To embark on this type of transformation requires several elements
- A detailed knowledge of how they work and where there is opportunities for improvement. A simple gap analysis and interviews (not an audit) will give you the answers you need. The important thing is that you need management support for the change. In the interviews, you need the employees to open up and speak honestly. I pledge that management will see the results of the interviews but not who said what. It will be sanitized (made anonymous). Trust has to be there.
- You must have a good interview skill. If you have gone through Kepner-Tragoe training you are well on the way. The key is to keep asking why. If you have kids, you know what that is. It’s the 6 year olds approach to learning. “Why is xxxx daddy?” You answer and they respond “Why is YYYY daddy?”
- You must listen and think how all the outcomes link back to behavior which then links back to the systems that are not working or are in need of improvement.
- And above all Management support for the change. They have to understand why the old will not sustain them and the new might and they must create a blame-free culture where speaking out is the norm.
It reminds me of the old realty axiom.
Its all about
Location, Location, Location.
here it is
Management, Management, Management
It is these system failures that help you solve things and change culture. Pick a key system that is not operating well (and everybody knows which ones they are), create a team of owners and customers and start a discussion forum for all to articulate the frustrations. Don’t let it get to a simple whining event. List the issues and ask how we might do it differently. Let each articulate with asking the rest to see if they have contributions. Facilitation skills are critical at this stage.
These suggestions can then be used by the system owners to revamp the process. Get the stakeholders in on the review. The first rendition will not be perfect but I bet it’s better than what was there.
So what is the new Quality style?
Its where Quality is
- Value added
- A facilitator 95% of the time
- Encouraging of partnering
- where user-centric systems, processes, documents are the norm
- where team based approaches are encouraged
- consulted to solve problems.
As you begin the make the changes, it is essential to get to the point where old habits are delearned and new ones embedded. It is aided when training becomes education and the HOW and the WHAT are alongside the WHY in the training. People understand why the change has to happen and they buy off on it because they understand why doing it the old way is not as good as the new. They understand it because they are part of the solution. It was their idea. They understand the consequences of their actions. They take ownership.
This is just the beginning. Watch for more blogs on next steps. The successes and the set backs.
By the way, the client’s ship has left the harbor. The captain has charted a new course (and its in the right direction) and the crew are all pulling in the right direction. Will it be plain sailing? I doubt it!! There will be storms and other testing events but the foundations are strong and they are determined. Tune in to see chapter 2.
So do you see any of the warning signs in your company? If so, you might want to drop me an email and let’s see what we can do!!!!!!
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
Both the EU and US have passed regulations allowing biosimilars. You know what they are. They are the copies of licensed drugs that have been developed by others. Somewhat akin to the generics of the drug world. The path to licensure of these biosimilars is more complicated than classic drugs. None have been licensed in the USA yet but they are off to a strong start in Europe and have been for several years where over 22 are on the market. Link to an article written recently on the topic on Master Controls GXP Lifeline e-journal.
In the first quarter of 2014, there are 3 warning letters for Indian Companies. Add to that the travails of Wockhardt and Ranbaxy over the last couple of years and it looks bleak for Indian Companies in general. I regularly read LinkedIn Groups and I noticed a thread related the question of reliability of Indian Medicines.
Can We trust Indian Drug Companies?
It created a firestorm of responses, many of which were from India. The responses fell into three categories which I will paraphrase
1. The FDA is picking on us – EU and US companies have the same problems
2. I would never take an Indian medicine again
3. Indan regulators find no problem who is the FDA to tell us what our standard should be
1. Of course some US and EU and other country companies have run foul of the law. Actually there are over twice the number of warning letters directed to Pharmacies than Indian companies in Q1. So maybe the FDA is picking on a broader range of companies. Or putting it another way – they are doing their job and hard one it is.
2. Are all Indian companies bad? Of course not. I do not know the statistics but I have heard that 50% (and it could be higher or lower) of the US generics is from India and undoubtedly the major are fine (at least I hope so).
3. I am sorry but if you want to sell drugs on the US market you have to play by the rules here. On paper, the Indian regulations are as tough as the FDAs but the question is detection of issues and enforcement that will separate the theory from the reality.
So what are the issues that are found
Smruthi Organics Ltd has a Warning Letter with only 3 observations. One centered on data deletion, record destruction and inadequate investigations. The link is here
Canton Laboratories Private LTD has a warning letter with 4 observations. The essence is failure to keep data from testing, failure to actually test, failure to adequately clean equipment and failure to manufacture according to instructions and keep adequate records.. The link to the Warning Letter is here
In reality there is a lot of similarity in all these observations. It does make one wonder about the quality of medicines. Is this the tip of the iceberg? Should I be worried?