The Calcott Consulting Blog:


Validation and monitors in shipping

July 8th, 2014 by

During a recent webinar I gave, hosted by Tungsten Shield Group, on the topic of Cold Chain storage and shipping, I was asked a question by an attendee.  It went this way:

Should I validate the shipping or can I just put a temperature monitor in?  What do the regulations require?

This question was interesting on two fronts:

  1. Do we do things to please regulators? and
  2. what is the purpose of validation versus verification?

I personally treat regulations as wisdom handed to us by regulators to help guide our thinking.  So I tend to turn the question of “what do regulations require?” into

What are the regulators trying to tell us?

I believe the decision to validate or put a temperature monitor in should be driven by what makes sense from a scientific / logical perspective and a business perspective as well.  The regulations are simply telling us that shipping can be risky and can put the drug into jeopardy.  Do what you can to prevent problems from occurring and if not fully possible, at least understand if there is a problem.

So in the case of road shipment (or air for that matter), there are measures you can take to protect the product.  I recommend the following logic

  1. Validate what makes sense – the shipping container can be validated to hold product for x hours and an outside temperature of y degrees.  But what happens if the shipment takes longer or is exposed to temperature above the range in the validation?
  2. For things that can not be validated, put controls or measures to minimize the risk or at least measures to tell you if there might be a problem. In this example, you can not really validate the operation of a refrigerated truck.  So the measures you put in place are to assure the operation runs smoothly or at least you know what went wrong.  That might include training of the driver on the critical elements, having a contingency plan in place if the truck breaks down or loses refrigeration etc.
  3. For those areas where you want more assurance, you can add a temperature monitor as well to tell you if things were outside the validated ranges.  The data then becomes critical in assessing whether you should use the materials or not.

So what might trigger the use of a temperature monitor in addition?  If the product is valuable or in short supply, you want to know if it’s still OK.  That makes good business sense.  Similarly, if it is a clinical product, the risk to the trial results of using a suspect material is just too high.  I would include a temperature monitor so if an excursion of time or temperature occurred, I would have data on the condition of the product to justify using it or not.

From my perspective, I would prefer to delay a patient getting a clinical drug, especially in a Phase 3, until I was sure the material was acceptable than blindly dosing with a suspect drug where the conditions were unknown.

 

Putting Quality Agreements into practice

June 24th, 2014 by

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!!

Setting sail on a voyage to discovery – creating a culture change in your operations

June 6th, 2014 by

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

  1. 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.
  2. 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?”
  3. 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.
  4. 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!!!!!!

You thought the Indian companies were taking a hammering. Better look to the US Pharmacies

April 26th, 2014 by

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 PharmacyPallimed SolutionsWedgewood Village PharmacyTotal Pharmacy Services ,Avella of Deer ValleyVillage Fertility Pharmacy

 

Biosimilars are taking hold in Europe at least

April 8th, 2014 by

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.

The link is http://www.mastercontrol.com/pharma/Biosimilars-Establishing-Themselves-Europe.html

Happy reading