A Master Plan For Designing And Developing Pharma Manufacturing Operations

Todd and Todd talk to Paul Melamud, Director of Facilities/Utilities/Equipment Compliance, and Scott Collins, Director of Laboratory Operations and Compliance, with QPharma, Inc. about validating solutions and partnerships.

Interview transcription:

Todd S: Good afternoon and welcome back to Life Science Connect Radio. I am your host Todd Schnick joined by my friend and colleague Todd Youngblood.

Todd, we are just weeks away from New York City and INTERPHEX 2014. I am so looking forward to getting there and broadcasting from this great event.

Todd Y: Yea, I think going to the Big Apple is always having fun and having INTERPHEX there just is going to add to whole experience in a big, big way.

Todd S: Yea, well, based on what we're hearing it's going to be a heck of an event and we're going to learn an awful lot. Leading up to INTERPHEX Life Science Connect Radio will be bringing you some great conversations from some fascinating industry leaders.

Today's show is no exception. So let's get right to it. Say hello to our guests Paul Melamud. He is the Director of Facilities, Utilities and Equipment Compliance and Scott Collins who is the Director of Laboratory Operations and Compliance with QPharma. Gentlemen, welcome to the show.

Paul: Thank you Todd and Todd.

Scott: Thank you Todd.

Todd S: It's good to have you. Thanks for carving out a few minutes to join us. I appreciate that. Paul, I want to start with you. Give us a quick rundown about you and your background.

Paul: No problem. My name is Paul. I've been with QPharma for approximately six years. I'm the Director here of all of our facilities, utilities and equipment projects that we do for our clients.

I've got experience with pharmaceutical industry from both the brand name and the generic part of the industry as well as when we go to medical device and biotech. We've done everything from validation to regulatory services to quality projects.

Todd S: Outstanding. Scott, give us a quick rundown on you and your background.

Scott: Sure. I've been with QPharma now almost 20 years. We're in our 20th year of existence. I started out as a laboratory chemist in quality control then moved over to quality assurance and down into pharmaceutical production. Then I got into validation around '91.

Todd S: Todd, me thinks these gentlemen have some valuable experience to share with us. Paul, before we dive into our discussion at hand today take a quick sec and give us the 10,000-foot view of QPharma. What do you guys do? How do you serve your market?

Paul: QPharma got its start as a compliance consulting and validation solutions company here on the East Coast in New Jersey approximately 1994. We're actually, as Scott said, celebrating our 20th anniversary this year. We do both commercial services and sales and marketing services for our clients.

We're not just a one-trick-pony with validation or anything like that. We serve clients all over the life sciences industry; pharmaceutical, medical device and biotech.

We have about 120 employees. We're here in Morristown in New Jersey. We have consultants that are based all over the country as well in various regions, whether it's out in California or up in the Northeast, the Midwest, things like that.

Todd Y: Scott, I would like to just get a little bit more background. I've been around manufacturing businesses for my whole career and have a pretty good feel for what quality assurance is all about. In the specific field of life sciences manufacturing talk a little bit about what's different and what's more challenging and difficult.

Scott: Many companies continue to face challenges in that area. One of the biggest causes is ineffective approach to planning. Rather than having a master plan and plan everything out from the top down, some firms continue to plan individual portions of a project as opposed to doing an overall master plan to begin with and then work it in from the top down.

They will start at the bottom immediately understanding and to them having clarification of that they want to do, what they want to accomplish and just jump right into doing the work.

Some companies will also fail to look beyond their three-year plan and take the necessary steps to accommodate their own growth. They will have clearly in mind what they want to accomplish for the next couple of years and then set themselves up for failure when they want to expand beyond that.

Todd S: Walk the audience through why compliance, which is obviously how you guys spend your day and it's the important work that you're doing. Why does that matter? Why is that so important in what you're doing?

Scott: The answer is the FDA enforces the compliance. It's the law that they have to follow. We will come in and answer the questions that the FDA asks them.

If they don't properly follow the regulations and be compliant with the regulations, then the FDA will hit them with finding, whether it be a 483 or warning letter or consent decree, and then we will help them interpret what the FDA is looking for and help them solve their own problems.

Todd Y: One of the things also that I've noted over the course of my career is a lot of manufactures will, in addition to buying new equipment when it's necessary, often get equipment both in the production line and in the laboratory that's been used. Is that a bad idea, a good idea? Does it matter?

Paul: I can answer that for you Todd. I'm sure you've bought cars before, right. I've own plenty of perfectly good used cars as well as new ones. But, I'll tell you the pitfalls are pretty much the same whether you're buying something that used for pleasure or buying one for business purposes.

One of the most common pitfalls related to equipment that we experience on our client projects is when purchase is usually urgent because management has decided that something needs to get done at a moments notice either because something broke and they can't make a product that's coming on backorder or maybe an expansion is suddenly critical and they didn't properly plan for it.

In order to accommodate the priority, they throw a lot of the good project practices out the window. Things like critical requirements gathering and getting your expert technical folks to evaluate a piece of equipment.

When these get neglected, usually nobody thinks of them until after the piece of equipment has been purchased and brought on site. So, I've got to tell you that kind of problem makes me think of something from recent memory.

We had an old blender at a client that was failing the calibration and they had determined that its control system was pretty much shot. It was a pretty old blender at that point in time. They could not really repair it and they did have a product that was going on backorder very quickly.

The site's production VP, who was no slouch, let me tell you, he was very well versed in all these unit operations for manufacturing. He knew what he was doing. He went out and he said, "I need to find this exact make and model of a blender and as long as I find that it's going to make my change control and it's going to make my validation activities much, much simpler."

 He went and he did that. He found it off-site somewhere. He found a blender that was the same model. While they were waiting for this thing that he cut a quick PO for they had to blow a wall out from the facility just to be able to get the thing in and install it.

When it was all said and done, when the dust literally settled, they spent about $100,000 just to get this thing plugged in without ever having laid eyes on it. It was really, really quickly thereafter when they first let the technical services folks come in that they realized that the drive was different and they had a number of other problems that basically told them they had to validate this thing from scratch.

They could not get away with all the efficiencies they thought they were gathering. I've got to tell you when we did our lessons learned on that project what really came to pass was technical services turned and said, "The couple hundred thousand dollars we spent on this we could have actually bought something new and got it done with the same amount of work in a quicker period of time and for less money."

I guess my lesson for that story is when you're looking at buying something used you shouldn't throw the good project activities out the window.

You really need to consider all of the things that make your process important, consider what makes your product a proper quality, and then include that as part of your purchasing decision. Don't go out and do it rashly.

Todd S: Let's take that a step further in terms of validation planning and execution. I'd probably like to ask both of you to weigh in on this but share some additional best practices the industry ought to know about.

Scott: The first thing would be to involve the entire team. A lot of places or a lot of companies, especially in production, when they want to buy a piece of equipment they'll just go out and look for it, purchase it and bring it in.

They don't let quality know that quality needs to develop the validation documentation to validate the equipment or system or they won't let IT know that they need to bring something online. The best practices involve the entire team while it's still in the concept phase so you can avoid very costly pitfalls further down the road on that.

Todd Y: Paul, a little different spin on that same question. Talk a little bit about the most common problems, issues and challenges you see popping up for your clients.

Paul: It's an interesting question in terms of what we see with our clients because everybody has a different experience. I think if I try to amalgamate all of the knowledge that we've got from the various projects we've been on, I think people changing their mind halfway through a project is probably one of the biggest things that you'll find as very common in the industry.

For example, our water systems. I've seen plenty of water systems where they get designed and they know that they want to put a certain number of use points for certain pieces of equipment and it takes several months to a year or more to buy the equipment and get it all laid off.

By that time, they've already got all these grand designs for different equipment and different use points. They just start throwing all these additional tie-ins to their system into the design but not always are they going back and looking at how this affects the pumps and the motors and the pressures and the overall flow rates and how many things can we use at a single time.

They will end up bottoming-out the system or not being able to use as much of the system at one time as they expected because they did not go back to the planning and do it all correctly.

I think to me that's one of the biggest challenges I see is you have all these people on these projects, everybody is trying to do the right thing, try to get things done quickly and sometimes we're just skipping out on these proper project approaches that we need to follow.

Todd S: You mentioned the FDA earlier in the broadcast. Talk about some of the current regulatory challenges that the industry is facing.

Paul: By that, I'm assuming you're talking about 483s and warning letters and things like that. Given that warning letters are already a filtered down version of 483s to what's really important and serious, I'm going to just talk about what we've seen as the trends in the 483s.

The past year or so, and I think the FDA collates it from third quarter to third quarter, there were, I believe, 5,200 483s that the FDA had put together. About 45% of those were food but when you look at the allied health care industries, 21 or so percent were devices, 18 to 20% were human drugs/biologics and then the rest were things like veterinary drugs and other ancillary things that the FDA deals with.

What shouldn't be surprising to your listeners though is that the trends of what the FDA finds for both devices and drugs are pretty similar. I went ahead and just grouped a couple of things together here in my notes so we that we don't go over 20 different versions of the same thing. I would say that the top five citations for drugs and the top five citations for devices accommodate somewhere between 80 and 95% of all the findings.

The things that we have seen and that the FDA has echoed, when you go through all of the data that they've complied, our number one issue is procedures not being fully followed.

A lot of companies put together procedures and for one reason or another people either think of improvements or think there are better ways of doing things and this doesn't get quickly through the procedure creation process. You end up having people doing things that are not written down.

The FDA considers that to be a very strong point of lack of control. Whose decision is it to make a change in the way you do something like that without it going through quality assurance and so forth and where do you draw the line. When the FDA sees things like that it tends to be a big warning sign. It is something that happens in a lot of different companies.

Second most common thing that they tend to look at and cite people for are poor investigations of discrepancies, failures and product complaints that come in from doctors and from people taking their drugs or using their devices.

What this really boils down to is the concept of determining an actual root cause. We seem to be getting better at it as an industry. There are still a lot of companies that I have been to where we've been brought in as subject matter experts because the people don't always know how to conduct a thorough investigation or in some cases are actually afraid at finding out what skeletons people have working very hard at keeping in the closet.

Nobody wants them exposed but once you understand what they are you can work with the quality departments and figure out what kind of impact they have and really, really act to never let them come out of the closet again.

Getting to the real root causes is something that is of very extreme interest to the FDA because when the same problems keep coming up again and up again and up again, these are the kinds of things that turn your 483s into warning letters. It shows that you're not in control.

Related to that would be the CAPA process, which is the third thing on my list here. The CAPA stands for corrective action and preventive action. What that really is is how do I fix the problem when it occurs and then how do I prevent it from reoccurring.

That's tied right into that root cause analysis I was just talking about. FDA expects you to not only get to that root cause and not only prevent it from reoccurring or at least plan for it to be prevented, but they want you to have an effectiveness review.

They expect that you have procedures that guide you through how you can verify that you really did prevent this problem from reoccurring so that you don't have just an infrequent accident waiting to happen again in the future when it could really impact product.

To me those are the top three and they all really fall on this idea of not following procedures and having deviations. The fourth and final thing that I have on my list relates to more of the scientific soundness of things. If you group them together, the FDA has cited both laboratory controls and process validation.

They have been cited because they're either not following their own SOPs or their master plans on how to do validation or how to do certain analyses in the laboratories but also sometimes that these validations that they draw conclusions out of don't scientifically support the conclusion that they say.

Whether that's because of poor statistical design or whether that's because they tried to cut corners and ended up not being able to prove something, those are the kinds of things the FDA says, "How are you saying you do good science when you don't have the documentation to support it?" I think that those four items are pretty much what summarized upwards of 90% of FDA's recent findings when it comes to doing inspections.

Todd Y:  Taking a different perspective, let's assume for a moment that I'm a plant manager and I'm looking for some outside help, some vendor that can help me with my quality and compliance. What process should I use and what kind of decision criteria should I use in choosing a partner to help me do all that?

Paul: Experience is a key as we've encountered throughout the years. You don't want a textbook validation or regulatory compliance person. They know what's written down but they don't really know how to apply it.

If you can find someone that has been out in the field experiencing it themselves who's worked in a pharmaceutical industry or medical device industry and who has done what we are trying to do at this point in time and who is now willing to share that experience and help us succeed in our goal.

The second thing, of course, you have to make sure you have to do is make sure they follow through with your supply or qualification process. Bringing someone like that inhouse without following your own procedures would just lead to one of the 483s that Paul has just mentioned.

Todd S: All right. Gentlemen what I want to do before we wrap here is ask each of you to give me a quick read on some trends, some things that we should be keeping an eye on, what the industry should be paying attention to with regards to validation planning and execution and quality. Tell us what you think we should be paying attention to.

Scott: Okay Todd I'll start and then Paul can add in with what he's experienced in the industry. For little over a decade the biggest focus has been on quality systems.

The FDA will come in and when they start an audit they'll look for your quality manual then your policy and procedures underneath and then any proof that you are following that. That pretty much has been leading to a lot of the 483s that Paul had mentioned previously around having good quality systems in place, following your procedures and proving that you have been following them.

Paul: Yea, I mean I think the quality systems approach is really where the trend has been. It's been that way for a few years and it's only getting more and more that way.

The way the 483s have been collated by FDA, the way they come in and start looking at say the quality management/quality system and then looking at one or more other quality systems and then judging the company based on those in deciding if they need to look at other quality systems.

For instance, if you want to be ready for an inspection, your quality people should already be ready for what has changed since the last time the FDA has come in. What organizational charts. I want to see your deviation lists, especially your critical ones.

I want to see your complaints. I want to see any recalls. I want to see change controls, I want to look at lists like that, and I'm going to start looking at them on a risk-based fashion. I want to see the biggest impact types of things.

I want you to start walking me through the documentation and if I see that you've done the big-ticket ones well, I'm going to have less worry about the other ones like the medium and the minor ones that don't really matter in terms of impact to patient but do show that you have a robust and properly functioning system.

The more risk-focused that you give to your internal audits to things like that and the more you try to highlight these items, the more ready I think that you will be for an external audit.

The FDA less cares about single individual findings as they do with how willing you are to respond to them, how readily you are able to respond to them and that your systems are overall in compliance and in control.

Because a system that's in control can at least give them the confidence, they need to say that this company is able to make good product on a standard basis.

Todd S:  All right. Gentlemen, thank you so much for sharing those insights. I hate to say that we're about out of time. Before we let you go, how can people get in touch with you and learn more about the work you're doing out at QPharma? Scott, we'll start with you.

Scott: They can reach us at www.qpharmacorp.com on the internet and they're more than welcome to come to Morristown, New Jersey to visit us. We're on 22 South Street in Morristown. Our number is (973) 656-0011.

Todd S: All right. Outstanding. Gentlemen, it's been a real pleasure to spend some time with you. Thank you so much for stopping by and joining us. I want to thank Paul Melamud, the Director of Facilities, Utilities and Equipment Compliance and Scott Collins, the Director of Laboratory Operations and Compliance with QPharma. Paul, Scott, thanks again for joining us. It was a real pleasure.

Scott: Thank you very much. It was a pleasure to be here.

Paul: Thank you guys.

Todd S: That wraps today's show. We'll enjoy seeing you at INTERPHEX in New York City March 18th through March 20th. You can catch Life Science Connect Radio broadcasting live from booth 1265.

On behalf of today's guests, Paul Melamud and Scott Collins, my co-host Todd Youngblood, I'm Todd Schnick. We'll see you soon on Life Science Connect Radio.