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Tuesday, May 8, 2012

Establishing Quality Systems: The Importance of Partnership

Written by Dawn Gabriel, Ph.D., Director of Quality and Compliance, QPharma

A quality management system can be defined as the organizational structure, procedures, processes, and resources needed to implement quality management in an organization. By establishing a quality management system, a company ensures that its processes are robust, and that its systems function as they were designed while addressing customer needs, complying with applicable laws and regulations, and meeting internal company standards.

The foundation that leads to a comprehensive quality management system has many elements. It is a given, for example, that a commitment to proactive, continuous improvement must be integrated into the culture of any company that strives to maintain an effective system. It is necessary to have the proper expertise on staff, to cultivate a Quality culture, and to keep current on the latest regulation developments, as well as industry best practices and trends. Periodic auditing is also essential, both internally, on the products and services delivered by in-house resources, and externally, on the contractors and other third-parties working on your behalf. Equally important is a validation process to verify that your systems are compliant and function according to specifications.

There is one element that is not part of processes, procedures, or systems, but that I consider an integral component of a successful and effective quality management system: a continuous focus on partnership.

In my career as a Quality Leader, I have always built partnerships with different business functions and units. This is accomplished through spending time with business stakeholders, and by demonstrating — through actions and decision-making — a collaborative and flexible approach to solving problems to meet both compliance and business needs. In a previous position, I received an “Innovators Circle Award” from a senior business leader for the partnership approach I demonstrated in identifying effective solutions to problems.

When colleagues and customers view Quality personnel strictly as an enforcement entity, the relationship between them will not foster compliance and continuous improvement. That is why, when QPharma is helping its clients in the life sciences industry to implement their own quality management systems, I work to instill a culture of partnership in my team that emphasizes the importance of listening carefully, keeping an open mind, and avoiding black-and-white thinking. By adopting this approach, we can help colleagues and customers remember that Quality’s role is to help — and to advance the goals and mission of the organization.

Tuesday, February 21, 2012

Selecting an Alternative Sampling Provider: Considerations for Brand Managers

Written by Michael Milunec, Director of Operations, QPharma 

As the industry evolves, pharmaceutical and life science product managers find themselves increasingly having to consider alternative sampling as a component of their marketing plans. It's usually a good fit for controlled substances and products with special handling considerations, but there are other good reasons to consider alternative sampling. For some companies, it's a marketing strategy that offers another opportunity to get a healthcare provider's attention. For others, it's a way of avoiding the accountability and compliance issues associated with requiring sales representatives to carry physical samples. Whatever the reason, it's important for brand managers to look for an alternative sampling partner that can meet their needs in a cost-effective and compliant manner — and that means asking the right questions.

How large is your pharmacy network?
An affiliation with a robust, nationwide network is important, simply because it translates to a better experience for the patient. Remember that with an alternative sampling program, patients are not receiving actual product samples; rather, they are receiving vouchers or co‐pay cards that they must redeem at a pharmacy. Whether that pharmacy is a major chain or a local drugstore, you want to ensure that your patients are able to receive your product regardless of where they go.

What is your average drug reimbursement rate?
The industry standard for determining drug reimbursement rates is currently driven by what is known as “Wholesale Acquisition Cost” (WAC). Desirable reimbursement rates tend to be between WAC+9 percent to WAC+10 percent. Better reimbursement rates can translate into cost savings for both drug makers and patients.

How extensive are your reporting capabilities?
Most vendors provide some level of online reporting, but few clients actually take the time to log on and generate reports. My clients like to have their reports pushed to them by FTP or encrypted e-mail. It gives them peace of mind to know that an account manager is reviewing their data and is available to point out trends and potential pitfalls. Most clients also appreciate a partner who has the ability to provide activity reports based on individual sales territories, and can generate reports that comply with federal and state reporting guidelines.

Can you provide client references?
When evaluating a potential alternative sampling partner, don't be shy about requesting to be put in touch with some of their current clients. A reputable, world‐class vendor should be able to provide a few contacts with confidence. Ask these references whether they like working with the company you're considering. Ask whether the company meets deadlines, whether they're knowledgeable about the regulations, and whether they're proactive in support of their clients’ goals and objectives.

By doing their homework, product managers can ensure that their alternative sampling programs are capably and professionally handled — with outstanding benefits for the company and the consumers they serve.

Monday, May 16, 2011

Don't Worry…After All, What Can FDA Do to Us?

Written By:  Jeff Boatman - CQA, Senior Subject Matter Expert, Quality Systems, QPharma

Quite a lot, actually!

Something that I often hear as I travel around the country preaching quality systems, Agency guidances, and Best Practices is some variety of: "I read the regulations and it doesn't say we have to do that so we won't." Often, the person making that pronouncement is a lawyer or an MBA with little experience in the real world of regulated industry and who has no personal knowledge of the range of tools that FDA—or any regulatory body—has at its disposal to make life difficult for recalcitrant firms. I’ll recap some of these, both from the news and my own experiences, in the hope that the reader may learn that instead of asking “how do we fight them,” perhaps the correct question should be “why are we fighting them at all?”

Don't get me wrong; FDA is made up of people who misinterpret requirements, let emotions and personal agendas color their decisions, and are just as bullheaded and plain wrong as anybody else. I’ve had my disputes with them, in fact I’m in the middle of arguing a client’s point right now. But when a consultant who’s been in industry for 20+ years makes a recommendation, or FDA writes a Guidance or a Compliance Guide, there’s usually a pretty good reason for it and perhaps your time might be better spent trying to understand that reason, and why it does or does not apply to you, than arbitrarily deciding “I don't have to do that so I won't.”

1. Greasing the Skids

This leads me to my first example. In my Quality System Regulation training, I used to recommend to all my medical device clients that they register with FDA while they were still in the design control phase. After all, it didn't cost anything (at the time) and was one less thing to worry about later on.

Well, of course a client—more specifically, a client's lawyer –looked up the regulation and noticed “oh, it doesn’t require registration until 30 days from commercial distribution. We’re nowhere near that so we don't have to do it.” And of course, they never came back to the consultant (me) for whose practical, real-world experience they were paying, to find out why they might want to register even if the regulation didn’t require it.

A few months later, I got a panic call from the client – the U.S. Customs Service had put a hold on their desperately needed materials for an ongoing clinical study. You can probably guess why: Customs had checked their database and found that the company had no FDA registration number! Fortunately, I knew the FDA liaison at the Customs’ office in Port Elizabeth and was able to get the product moving with minimal delay. So here's something that the consultant knew, but which you won't find in any regulation: having a registration can help get your materials through Customs. (Note that since FDA now charges to register and to re-register, I no longer give this blanket advice; but it is still something worth considering.)

2. The “Guidance” Document that's Anything But

If there’s one source of pushback I get from clients that tops the list, it’s that they don't have to follow an FDA guidance. Mind you, if I heard that they don't have to follow a guidance because they've analyzed the document and found that it does not apply to them—or that they already employ systems that are even better—I’d be very happy.  Unfortunately, that’s rarely what happens; it’s usually “if it’s not in a regulation then we don’t have to follow it.” Au contraire – if it’s not in a regulation then perhaps you cannot get a 483 for not following it (maybe – try telling that to the authors of FDA’s new guidance on Process Validation), but there are all sorts of examples why that attitude is less than helpful.

For example, FDA has a guidance document on hemodialyzers; if you follow that guidance, then your product will be classified as Class II and you can market it on a 510(k) clearance, which is a far cheaper and faster way to get to market. If you don’t follow it, then to be sure, FDA cannot cite you and the Justice Department will not show up to handcuff you…but your product will automatically become a Class III device, requiring Premarket Approval and millions of dollars and years of extra work to market.

A similar and more general guidance is the one for Part 11. On many of my audits, I’ve made observations that firms don’t have inventories of their computerized systems and written risk assessments. “That’s not in a regulation, so we aren’t going to do that!” That’s absolutely correct – and absolutely self-defeating, because having those inventories and risk assessments allow you to reduce your controls and validation coverage below that strictly required by 21 CFR 11.10, 11.50, and (arguably) 820.70(i). By refusing to follow the guidance, you are condemning your firm to have to follow the strict and (even by FDA’s own admission) sometimes absurdly onerous requirements that are in the regulation.

Speaking of Part 11, I remember a statement in one of the drafts floating around in the early 2000s. Now this was not only a guidance, it was a draft. Surely it carried no weight! Until you read the clause “This draft guidance is used by FDA staff in conducting inspections.” There’s nothing “optional” about that at all – that document told you what the FDA inspector will be looking for, so shame on you if you ignored that invaluable information!

Finally, on January 15th of this year, FDA issued a Final Guidance on the subject of registration of tobacco products. This document, clearly marked “CONTAINS NONBINDING RECOMMENDATIONS” (hah!), set forth the rules for tobacco manufacturers to get in their “905(j)” submission reports within three months (i.e. by this past March). Companies that failed to do so in accordance with the guidance are guilty of selling misbranded product, liable to confiscation and legal action.

“Nonbinding” my eye!

3. The Mystery of the Mandatory Optional SOP

Here’s an example of why you sometimes need to find a true Subject Matter Expert, and not just tell an employee to “go read the regulation.” Under 21 CFR 820.30, manufacturers and designers of Class II and Class III medical devices must have written procedures for design inputs, outputs, verification, validation, review, and transfer. 21 CFR 820.30(j) requires you to maintain a Design History File on your product. But nowhere does it say that you must have a procedure explaining how you maintain that file. So if you don’t have such a procedure, FDA cannot possibly write you up. No 483, no Warning Letter, no Consent Decree.

Of course, just because you are not gigged for a regulatory violation doesn’t mean your submission will actually get approved, and in this case it won’t.  That’s because buried inside FDA’s guidance (yep, yet another guidance document) on quality information submitted in Premarket Approval applications is a list of procedures that must be provided before FDA will review your application…and your procedure for maintaining your Design History File just happens to be one of them!

4. Obey the Law

“Finished dosage form” pharmaceutical companies must produce drugs in compliance with the Good Manufacturing Practices of 21 CFR 210/211. It says so right in 210.1(a) and 210.3(a)(3). It doesn’t say anything about the vendors of the drug firm, though. Sure, there is an expectation that a drug firm ensures that their vendors provide quality products meeting their expectations (that whole “safety, purity, identity, and quality” thing, plus there’s an implied expectation under 21 CFR 820.50(a), applicable to a drug firm under 21 CFR 820.1(b) – you did know that, right?), but surely FDA cannot directly cite a vendor if the regulation doesn’t give them that authority.

À nouveau, au contraire! FDA regularly inspects Active Pharmaceutical Ingredient manufacturers and cites them against Part 210/211, as guided by ICH Q7A (yes, another of those pesky guidance documents)…because the predicate Safe Food, Drug, and Cosmetic Act’s definitions of adulterated (21 U.S.C. §501(a)(2)(B)) and drug (21 U.S.C. §201(g)(1)) authorizes them to do so.

5. Recalls, Recalls, Recalls

In case you missed this, FDA just got sweeping new authority to preemptively order recalls of food products. Prior to 2011, FDA only had such statutory authority over a narrow subset of foods (baby formula, acidified canned products); they’ve also had this authority over medical devices for years. This underlines a common confusion about which regulations actually cover recalls: generally, they’re described in 21 CFR 7, but because Congress has granted FDA preemptive authority over various industries over the years, Part 7 is often supplemented by an industry-specific regulation (in the case of devices, you’ll find those additional regulations in 21 CFR 810).

There was a move to include preemptive drug recalls in the Food Safety Modernization Act but it got dropped…for now. I expect the McNeil situation to re-ignite this debate in Congress, which had quieted down a bit since the last person was killed by adulterated heparin.

6. Miscellany

FDA’s ability to order recalls—along with their power to refuse or rescind Certificates of Foreign Governments, detain product at Ports of Entry (as opposed to outright confiscation requiring court order), suspend Clinical Trials, and their greatly underappreciated ability to pick up the phone and call Labor, EPA, OSHA, Customs, etc.—has rarely been diminished during their entire history and in fact continues to increase with time.

Often forgotten is the fact that FDA has non-judicial administrative options beyond just the approving or clearing of products, especially the rarely-invoked but powerful federal debarment of individuals. Think debarment is just a personal matter? Consider FDA’s recent move to debar the CEO of Forest Labs in connection with marketing shenanigans – if he is debarred, then he must either leave company management or Forest will lose its ability to submit for federal reimbursement from sCHIPS, Medicaid, Medicare, and Veteran’s Administration programs – money that few large pharmaceutical companies can survive without.  FDA’s stated stance is they can debar him irrespective of proving his actual knowledge of wrongdoing because debarment is not a legal proceeding. As FDA chief Margaret Hamburg continues to look for outside-the-box ways of bending wayward firms to her will, I expect to only see more actions like this because FDA is simply not seeing companies change their ways in response to mere fines.

7. When You Can’t Beat ‘Em, Join Their Competitors

Speaking of outside-the-box thinking, I’ve saved for last the item that triggered this blog entry.  Consider KV Pharmaceuticals: GMP issues, recalls, FDA inspections, 483s, Warning Letters, Consent Decree, third-party oversight. FDA essentially shuts down their operations, two of their three divisions promptly go out of business, several rounds of layoffs. Income stream is, well, challenged.

In a move no doubt intended to inject some much-needed cash, KV buys the exclusive rights to distribute a prenatal care medication, Makena, an Orphan drug that provides critical health benefits and for which there is no real alternative. Note that KV is a generics company, so this is something of a foray into the tradename business for them; patent owner Hologic developed the drug in conjunction with NIH.

The medicine in Makena was a true bargain at $20 per injection. KV decided to raise the price a little: $1,200 a dose!

FDA doesn’t regulate pricing, so what exactly can FDA do about this? Here’s what: FDA just announced that they intend to exercise “enforcement discretion” against pharmacies that compound their own version of Makena and sell it to prescribers. It’s unclear what recourse KV or Hologic may have in suing these pharmacies for intellectual property violations, but with this announcement FDA has basically declared open season on KV by promising that if you make your own version of Makena (and presumably don’t sell it for $1,200) then FDA will not go after you for misbranding.
I bet KV management didn’t see that one coming!


All too often, I find that Top Management of Life Science firms believes that the best and most cost-effective strategy is to always do as little as possible. That top-level philosophy inevitably trickles down to middle management and brews a culture of noncompliance – spend your time on figuring out ways to avoid complying with FDA’s recommendations rather than efficient ways to implement Agency expectations.

In my nearly quarter-century in this industry, I have yet to see a single instance where this approach actually worked, but I have seen countless cases where it backfired in ways that management never dreamed of. In the March 2005 Gold Sheet (volume 39, number 3), no less a personality than David Elder, Director of Enforcement for FDA's Office of Regulatory Affairs, said it best:
“If we ask a question and the answers are so guarded that they are one-syllable answers, you are creating an impression. When you could clarify something, but choose not to under corporate policy or advice of counsel, you are creating an impression. I do not know if it is doing you any good, because you are extending the period of time we will be there...if we do not get the full answer that we are looking for, we are going to ask the question six different ways, and on different occasions.  The people that are proud of their operations...have nothing to hide.”
When FDA finds that a firm goes out of its way to avoid adopting best practices and Agency recommendations, that creates an impression. Impressions are formed by strategies, strategies are formed by culture, and culture is established by management’s attitude. If Top Management doesn’t understand that FDA has ways of punishing them that go far beyond anything taught in an MBA class, they may be dooming the very business objectives they are trying so hard to achieve.

Monday, May 2, 2011

The Twelve Towers - A Project Management Novel: Excerpt 3 – The Project Management Plan

Written by Bruce Fieggen - V.P. of Project Management, QPharma

Below is the third excerpt from the Project Management novel Bruce Fieggen, QPharma’s V.P. of Project Management, is writing in his ‘spare time’. The novel tells the story of a Gwilym, a Project Manager, charged with building twelve towers scattered throughout King Arthur’s Britain. Gwilym’s assistant, Fred, also appears in this excerpt. This excerpt takes place in chapter two of the book, a year after the previous excerpts and after the first tower is completed. 

Readers, think about the various projects you are tasked with and see how you can use the tools shown in these blog posts to assist you in ‘building your towers’.

This third excerpt shows the beginning of the development of the third tool: The Project Management Plan.

The next morning, as they loaded their cart with their few possessions, the largest of which were the two scroll boxes, they were happy to see Fred ambling up the road, leading a laden pony. “Tha were serious last night, weren’t tha? Me ma said tha were just bein’ kind, and that I were a fool to believe tha.”

Gwilym clapped the man on his shoulder and told him to pack his goods in the wagon and tie the pony behind. “We’ll all be comfortable in the cart together.”

The three of them picked up the pallet, together with the sleeping babies inside and stowed it safely in the space left between the boxes. With a last look on the quiet village, they headed off on the eastern track to meet the Roman road.

The cart was not heavily laden so they made steady progress but the bumping threatened to wake the babies. Fred was getting more anxious and finally burst out, “Tha knows I’m t’better driver. Give me t’reins.” Taking these from Gwilym, he steered the cart around all the bumps in the road. They traveled away from the coast and through a country unspoiled by Saxon raids. While Bleddyn stared silently at all the new sights around him, Gwilym and Bleddyn discussed the new project.

“I’ll know more when I get on the site, but Sir Kay has given me a new charter that explains a lot. He likes these charters and gives them out to all the new builders.” Gwilym smiled at Fred who touched his nose significantly.

“That were a great idea of tha, gettin’ it all written down so none could argue. So what do this one say?” 

“Well, it’s curious. They want a watch-tower; I suppose it is one of a series of watchtowers leading from the north coast inland to warn of marauding Norsemen. But if it is just for passing on signals, why is it built to hold a garrison of men and to be defensible? There is a ferry there across the Ouse, so perhaps it needs to defend the ford? We’ll have to see when we arrive.”

“And how will we be makin’ this tower better than t’last one?”

Gwilym thought long and hard. “There were a lot of problems last time and they seem to all stem from not knowing exactly, what everyone wanted. The charter showed what the king wanted, and I did well following that exactly, but I think instead we need more of an overall understanding from the king, and allow the people who will be using the tower and the people who have to build it to have some say in what the real requirements are. And from there we can figure out exactly what we are doing and how to get it done.”

Fred was humming softly to himself and thinking hard about something. “What were you just doing?” asked Gwilym when Fred seemed to be finished.

Fred blushed deeply and mumbled, “Oh, just trying to remember what tha told me.”

“Please explain.”

“Well, tha knows I cannae write. I’m too stupid for that. Even your son can write and here I am, a grown man but too stupid. So I remember things by songs. I know, it be stupid but it’s me only way.”

“Fred. You’re not a stupid man. I’ve seen you grasp the concepts of building faster than any other man I’ve worked with. Ignorance of the skill of writing is not stupidity. Men were remembering things by song long before someone thought to write them down. These scrolls I carry are just the written words of long-ago songs. But sing me your song about tower building. I’d be privileged to be your first audience.”

Fred alternated blushing and smiling and stammered out that it wasn’t a song about building towers. “I figure that t’song would work for any kind of buildin’, any kind of project for that matter. It be a song about gettin’ a group together and doin’ sommat…when they be not thy men…when tha not be in charge of them tha see?”

Gwilym smiled in genuine respect and asked the man, “Sing me your song. I think I could learn a lot from it.”

“Tha be the one teachin’ me. I’m just rememberin’ it. T’song’s not ready yet but I can give tha a taste for it.”

“Please do.”

If you want your project to be no harder
Go to the king to sign your charter
Make sure it says how small or large
And says quite clearly that you’re in charge
It should show how it meets the kingdom’s need
And keeps all the others from their greed
It went on like this for a while, describing the charter, the list of stakeholders and some awkward verses about scope and requirements. Fred stopped then and said he had to work out those last verses better when he knew more about them and had seen how they work.

“Fred! You’ve done a great thing here. Please keep building on your song. When it’s done you’ll have the guide for Project Management. I can write it down for you in a scroll and you’ll be famous as a teacher of future Project Managers.”

“Ach! Tha’s just havin’ fun wi’ me now. Leave off.”

“No Fred. I’m quite serious. You’ve created something important. Please do keep it going.”

If you are enjoying the excerpts and would like to read more of the story in order, go to to read the first five excerpts. A new excerpt appears here every two weeks

Monday, April 25, 2011

What’s The Deal with McNeil’s Consent Decree?

Written by Clinton Ballard - Validation Specialist, QPharma

After nearly 2 years of recalls totaling more than 47 million units of very popular over the counter (OTC) drugs (Sudafed, Tylenol, Rolaids, Sinutab Sinus, Benadryl, Motrin, and Zyrtec) on March 10, 2011 McNeil-PPC, Inc. subsidiary of Johnson & Johnson Services, Inc. (J&J) signed a consent decree with the FDA covering manufacturing facilities in Las Piedras, PR, Fort Washington, PA, and Lancaster, PA.

The details of the Consent Decree requires McNeil to destroy all drugs under their control that have been manufactured or recalled from the Fort Washington, Las Piedras, and Lancaster facilities since December 2009 to the date of entry of the Consent Decree. McNeil is allowed to continue manufacturing operations in the Las Piedras, PR and Lancaster, PA facilities but manufacturing and distributing drugs from its Fort Washington, Pa., facility is prohibited until the FDA determines that its operations are compliant with federal regulations. McNeil must comply with a stringent corrective action plan across all three sites set forth by the FDA. The full details of the corrective action timetable are outlined in the Consent Decree. The key arrangements of the Consent Decree requires that McNeil establish and implement a quality assurance / quality control (QA/QC) program that is applicable to cGMP regulations and in coordination with J&J’s corporate level QA/QC program. McNeil is also required to hire an independent cGMP expert to: inspect all three facilities to determine whether the violations the FDA found during their audits have been corrected, ensure that proper manufacturing processes are in place, and verify that the agreements made in the Consent Decree are met. After certification from an independent expert, the FDA will determine if the facilities are in compliance. If McNeil maintains all three facilities in a state of continuous compliance with applicable regulations and the Consent Decree for at least sixty (60) months they may petition the courts for relief from the Consent Decree. 

McNeil is required to pay the cost of all of the FDA investigative expenses while under consent decree. As of the date of entry of the Consent Decree the cost of FDA inspection is $87.57 / hour, the cost for any laboratory work is $104.96 / hour, and $0.51 / mile for travel. If McNeil violates the agreements of the Consent Decree, the FDA can order McNeil to cease all manufacturing, recall products, and take other corrective action, including levying fines of $15,000 for each day and an additional $15,000 for each violation of the law, up to $10 million annually.  

 J&J will end up paying a nice chunk of change for their McNeil sites’ failure to comply with federal regulations. But, considering the repeated recalls and how long the FDA has been telling McNeil, to clean their act up McNeil got off rather easy based on the agreements of the Consent Decree. McNeil is not required to cease production of any of their recalled products which is usually agreed upon in most FDA consent decrees. McNeil was also able to circumvent paying a hefty disgorgement fee like Schering-Plough who signed a consent decree with the FDA and was required to pay $500 million dollars to the United States Treasury back in 2002. J&J CEO, Bill Weldon was also not listed as a defendant on the Consent Decree but in past consent decrees involving Schering-Plough, Abbott Laboratories and Genzyme the CEO was listed as a defendant. In McNeil’s case the Vice President (VP) of quality and the VP of operations for OTC products are listed as the defendants. Essentially this Consent Decree is a slap on the wrist for McNeil and merely shines light on the implicated McNeil sites’ lack of commitment to “high quality” as stated in the J&J’s corporate company credo.

J&J is a leader in the healthcare product industry, reporting $61.6 billion in sales for 2010. OTC pharmaceutical sales made J&J $4.6 billion in 2010 accounting for 7.7% of their total sales. Recalls were estimated to have cost J&J $900 million in sales in 2010. Considering the amount of money on the line and the brand J&J has created with their McNeil Consumer Healthcare product division it would not be in the company’s or stockholders best interest to not come out of this Consent Decree as a transformed company with a newfound commitment to the J&J Credo. 

The transformation has already begun. Recently J&J has announced that they will be splitting the McNeil Consumer Healthcare unit up into divisions by geography and product type, allowing for more focus on consumer drug operations. Under this new infrastructure, the product lines will be organized into four categories: OTC drugs, skin care, oral care and women's health. The regional divisions: Asia-Pacific, North America, Europe/Middle East/Africa and Latin America will market all of the product lines.

Fortunately J&J can afford the cost of coming out of a FDA consent decree, but do they have the necessary internal McNeil leadership and support required to guide them out of this Consent Decree is a question that only time can answer. Stay tuned as we continue to monitor J&J’s attempt to come out of this Consent Decree.