What Suprises GCP Auditors?

Last month, I scheduled one-on-one discussions with our most experienced GCP auditors to ask each of them the same question: What surprises you most about the audits you conduct?

I guess you could say that I was the one who was surprised. I’m not sure exactly what I was expecting to hear, but I thought my teammates were going to talk about things that were new. Instead, I heard a lot more about things that have been around for a long time. To a person, my colleagues said they were surprised to be observing some of the same audit findings they were observing 30 years ago...which *is* surprising when you consider most of them were mere children at the time. ;-)  It seems we have some stubbornly persistent quality and compliance issues in the biopharma industry that decades of neither experience nor technology have seemed to remedy. And the problems are not just persistent; they’re interrelated.

SOP Revision, SWAT-Style

By Laurie Meehan

SOP revision. It falls somewhere between income tax prep and colonoscopy prep on the likability scale.  So why would you want to read about it?  Maybe you’re hoping someone’s figured out a way to make the process more efficient and less painful.  Maybe we have.

The SWAT Technique

Last month, we worked with a company to revise a set of SOPs using a technique we call SWAT.  (Any edgy appeal that name might have otherwise had will be immediately dulled by its acronym expansion: “SOP Working Analysis Team.”  It’s the best we could do.  Don’t judge.)

The goal of the SWAT technique is to revise the most documents in the least time, while preserving friendships, sobriety, and original hair color.  The heart of SWAT is an immersive, multi-day working session in which participants discuss SOP revisions and incorporate them in real time.  Careful planning, thorough preparation, and commitment from management and participants are keys to keeping the SWAT session productive.

It’s Not For Everyone

Up front, we need to say that SWAT won’t work for every organization.  While the size of the company may not be important, the size of the working team needs to be fairly small.  Also SWAT won’t work for every set of SOPs.  The documents need to be part of a natural grouping – a set of similar procedures – and not a random collection.

But in the right situations, SWAT works very well.  Last month, we conducted a 2-day SWAT session with a client’s QA department to revise a set of 10 auditing SOPs.  We’ve also successfully used the technique with ClinOps teams, for example, to revise sets of monitoring SOPs.

SWAT Planning and Preparation

The SWAT process begins with central planning.  A coordination team selects a logical grouping of SOPs to revise, and assembles a list of specific revisions to be made.  Where it’s not possible to provide specific revisions, instructions and guidelines are developed, such as “remove audit report distribution details” or “update to reflect new file safeguarding practices.”

Each SWAT participant is assigned an SOP from the revision set.  The participant doesn’t need to be the author of record, but must be knowledgeable enough to “represent” the SOP – to learn the document well and understand how it’s similar to the other SOPs in the revision set and in what ways it’s unique.  Based on this understanding, prior to the SWAT session, participants make applicable revisions to their individual documents using the information received from the coordination team.  Participants should also note questions and any open issues appropriate for SWAT discussion using inline comments. 

SWAT Session

The result of the SWAT session is a set of approval-ready SOPs.  The precise structure of the SWAT session to get you there depends on a variety of factors, such as how similar or dissimilar the SOPs are, the extent and complexity of the revisions, and whether subject matter expertise is concentrated or distributed among the group.  But all successful SWAT sessions we’ve conducted share these attributes:

• Duration of 2 to 3 days.  Just long enough to accomplish the aggressive goal, just short enough to keep everyone from diving out the window.
• Real-time revision.  The “SOP of the hour” is projected on a screen while participants sit in front of PCs and update their assigned SOPs accordingly.
  
• Rigorous facilitation. It’s natural for discussions about company procedures to morph into other topics, such as business strategy or staffing requirements.  Discussion *will* get off topic.  When it does, the facilitator must act quickly to table it.  You can maintain a list of tangent topics on a flip chart, schedule a meeting to discuss the most pressing items, ring a cowbell, blow an air horn, or drop a quarter in the “Diversion Jar” and move on, but keep those conversations out of your SWAT session.  Save the war stories for dinner.
• Commitment to the process.  Scheduling the session is one thing, but remaining dedicated to the session is an act of will. It’s so ridiculously easy for outside work to creep in.  Management and participants must be committed to carving out the time and keeping the barbarians at the gate.
• Of course: Plenty of caffeine and yummy treats.

If you’ve ever worked on SOPs, you know there’s a big difference between done and almost done.  To help ensure you emerge from the SWAT session with the former, time must be allotted for participants to format, polish, and conduct a quality review.  If it’s possible to scare up some on-site administrative support, that could help expedite the process.

SWAT Benefits

When you look on your team’s Outlook calendar and see 3 entire days blocked out, it can seem like an awful lot of time devoted to SOP revision.  But SWAT really doesn’t take any longer than the usual process, it’s just more obvious.  Does SWAT take significantly *less* time?  Mmmm, not sure, but SWAT brings with it other benefits.

SWAT produces a more consistent set of SOPs.  Since every document is compared to every other, it’s easy to notice and correct incidental differences.

SWAT is a cross-training opportunity.  Participants enter SWAT knowing their own SOP very well.  They leave knowing the whole SOP revision set very well.

SWAT gets it done.  Auditors, how many times have you cited facilities for failure to revise their SOPs within the specified window?  It’s not because there’s a willful disregard for SOP procedures.  It’s because, in the real world of work, revising SOPs is seldom prioritized highly enough to get on anyone’s schedule until the end of the revision window encroaches or – oops – has passed.  But schedule a SWAT and they will come. (And because the effort is so visible and so obviously resource-intensive, no one wants to be the one to drop the ball.  Participants come prepared and the resulting documents are the better for it.)

SWAT is a lot more fun.  Revising SOPs on your own is really boring.  Revising them in immersive sessions with colleagues is significantly more enjoyable.  Gallows humor reigns supreme.  Copious amounts of chocolate are consumed.  Air horns are blown in celebration.  Friendships, sobriety, and hair color remain intact.  Participants live to write another day.



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Photo Credit:  Tenaciousme CoffeeArt, under Creative Commons License

One Q & a Lotta A’s about SOPs for Research Sites

By Laurie Meehan

Posted on LinkedIn in July:

“What are your thoughts about having SOPs for clinical research sites versus having working guidelines in lieu of SOPs?”

You know how it is with those LinkedIn discussion groups.  You think you’re posting an intriguing and brilliantly conceived question that will inspire your colleagues to clear their desks, seize their keyboards, and plunge headlong into enthusiastic electronic debate.  Instead, your post lands unceremoniously on the ground, with only the dullest of thuds, ignored and unloved.  So naturally, when I encountered the post above -- which had managed to attract 32 responses -- I was curious to see what had garnered such attention. (And yes, that was 3 months ago and I’m just getting around to writing about this now.  Don’t judge me.)

The CAPA Detective

By Laurie Meehan

Every industry has its detectives.  Mechanics and journalists hunt for leaks.  Software testers and security experts look for bugs.  Meteorologists, defense strategists, and forensic accountants all look for trouble brewing off shore.  The level of intrigue may vary.

In the GMP world, it’s the CAPA investigator who serves as detective, identifying how and why manufacturing defects occur.  The root cause is seldom obvious or sensational, but usually a confluence of seemingly innocuous deviations that can compromise an otherwise high-quality manufacturing process.  That’s not terribly flashy, so you probably won’t find “The CAPA Detective” in among the other crime dramas making their debut in this year’s primetime lineup.

Or maybe you will.

What If You Needed SOPs to Run Your Household?

Last week I traveled to Phoenix to videotape a presentation for Natural Products INSIDER’s upcoming Digital Summit.  The 45-minute presentation, entitled “A Guide to SOPs and Compliance for Dietary Supplement Distributors,” goes into  much more detail than our February blog post on the same subject (which you can read here: http://bit.ly/YGTQWd).

Rosanne Sylvia-Heeter, Director of cGMP Compliance at Polaris, is always chanting the FDA compliance mantra, “If it’s not documented, it didn’t happen.”  As I worked on the blog post with her last winter, I was struck by the amount of documentation actually needed to comply with 21 CFR Part 111 distribution regulations.  As we worked on the Digital Summit presentation this summer, I was struck by something else.  In the course of simply maintaining a residence, members of my household actually perform a lot those Part 111 activities.  And so do yours.

The big difference is that we don’t have to write it all down.

Part II: What SOPs Does A Dietary Supplement Distributor Need?

Last summer, we received a lot of feedback on our post entitled “What SOPs Do I Need As A Dietary Supplement Distributor?”   To respond to your questions and comments about 21 CFR Part 111, we’re posting an expanded version of the original article.

If you look at the cGMP regulations for dietary supplements, you’ll notice that only 1 subpart includes the words “holding” or “distributing” in its title.  With only 10 or so individual requirements, the aptly-named Subpart M, “Holding and Distributing,” is shorter than most.  If you’re thinking this means there’s a much lighter regulatory burden placed on companies that simply hold or distribute dietary supplements than on companies that manufacture them, you’d be right.  At the same time, you’d be incorrect to assume that regulations for holding and distributing dietary supplements are restricted to this single subpart.  At least 8 of the 16 subparts that comprise 21 CFR Part 111 are applicable to holders and distributors, and all the activities outlined in these subparts require SOPs.

Subpart B, “Personnel” requires that your employees be qualified for the positions they hold and be trained in hygienic practices and warehouse operations.  Naturally, this training needs to be documented.  SOPs are needed to describe the procedures you have in place to comply with these staffing requirements.  That’s important, because as you read on, you’ll see the warehouse staff has a lot of responsibilities.

Subpart C, “Physical Plant and Grounds” dictates that your warehouse be clean and pest-free.  Dirt, insects, lubricants, or other agents could compromise the packaging or prevent labels from adhering.  Your facility also needs proper drainage, adequate space, and work lighting.  (Do cramped or dark conditions increase the likelihood of dangerous product mix-ups?  Is any of your product sitting directly on the floor rather than on pallets?)  You must also make sure that the product you hold is not exposed to more heat, cold, humidity, or light than the manufacturer recommends.  (Is the heat tunnel you use for sealing shrink wrap too hot?  Do you have backup refrigeration?  Is there sufficient ventilation?)

Any homeowner knows that conditions in a building are not uniform; buildings have hotspots, cold spots, and damp spots.  Just as the pharmaceutical industry has done, some dietary supplement holders are using a technique called “warehouse mapping” to help ensure safe product storage.  In warehouse mapping, the 3-dimensional warehouse space is logically divided into many smaller blocks, a sort of Rubik’s Cube.  Sensors that monitor temperature and humidity are placed in all 8 corners, the areas of the “cube” that are most subject to variations in environmental conditions.  Monitoring is performed at least seasonally, as temperature and moisture will fluctuate throughout the year in most locations.  Sensor data can help warehouse staff pinpoint specific areas of the facility that have inadequate ventilation or excess heat or moisture.  Additional fans, air conditioners, or dehumidifiers can then be deployed to remediate any adverse environmental conditions.

Subpart D, “Equipment and Utensils” discusses the care and feeding of all machines used to control environmental conditions, and to move, store, repack, or otherwise handle product.  SOPs describe proper cleaning procedures, permissible cleaning agents, and cleaning frequency.  (Could this cleaning solution cause labeling ink to fade?)  They describe inspection and maintenance requirements.  (According to the manufacturer, how often should this thermostat be calibrated?  How often is electronic inventory control data backed up?)  They outline installation and operational qualification procedures.  (Has your industrial scale been installed on a flat surface?  Is your packing peanut dispenser blowing so forcefully that it could damage labeling or product container-closure systems?)  Finally, SOPs describe all of the associated records that must be kept and the internal QA procedures to ensure it’s all being done. 

Because you cannot ensure the quality of the product you distribute without verifying the quality of the product you receive, holders and distributors must implement some of the measures identified in Subparts E and F which cover Process and Quality Controls.  The contents of incoming shipments must be confirmed against invoices and other paperwork, and applicable certificates of analysis must be verified.  Product should be visually inspected.  (Has any product reached or neared its expiry date?  Is any product damaged?)  SOPs which describe these activities, as well as the procedures for handling damaged/expired product must be documented and followed.

Since Subparts G through L apply only to manufacturers, packagers, and labelers, alphabetically we’re now up to Subpart M, “Holding and Distributing.”  Not surprisingly, this section requires that product be held in a manner that prevents its contamination and deterioration, and preserves its purity, strength, and composition. As we’ve seen, Subparts B through F outline many of the detailed regulations you need to follow in order to protect your products…but not all of them.  Temperature, ventilation, and moisture content are not just warehouse attributes; they apply to shipping environments, as well.  To ensure that product receives the same protection in transit as it received in the warehouse, distributors must conduct shipping tests at various times of year and over a variety of shipping routes. (Will our product survive the stretch of Interstate 10 between Phoenix and Tucson in the middle of August?)  Lastly, Subpart M requires that samples of each batch of product be retained for a specified period of time.  Holders and distributors should document and follow procedures for periodically reviewing the condition of the samples and for investigating the cause of any deviations discovered.  (Are the product labels legible?  Is the packaging holding up? What should you do if the the appearance of the product has changed during its shelf life?) 

Even after your product has been delivered, your regulatory obligations have not been fully discharged.  Subpart N, “Returned Dietary Supplements” outlines quarantine and disposal requirements you must follow and quality control responsibilities you must carry out when product is returned to you.  (Under what circumstances can we redistribute product?   What if the return is simply the result of excess retailer inventory?)

Subpart O, “Product Complaints” outlines your responsibilities surrounding any product complaints you may receive.  Remember those samples you’ve been storing according to Subpart M?  Get them out, because that’s where your investigation will begin.  Some of the activities here resemble those of a traditional CAPA program:  determine the root cause of the problem and take corrective and preventive action.  (What if the problem is not mine – what is the protocol for dealing with manufacturing, packaging, or labeling issues? What are my obligations if we receive an email from someone who claims that the product has made him sick?)    

Finally, as a distributor, you would likely play a key role in any product recall.
Subpart P, “Record and Record Keeping” enumerates the data you must keep in order to respond appropriately to a recall order (as well as demonstrate Part 111 compliance in general).  Conducting periodic mock recalls to test your recall SOPs will help ensure that inventory and distribution records provide the information necessary to successfully recall all targeted product.

Perhaps to those involved in pharmaceutical manufacturing or clinical research, the regulatory burden placed on holders and distributors of dietary supplements may seem light.  In fairness, comparatively, it is light.   But that doesn’t mean complying with all the necessary Part 111 provisions is easy or straight forward.  It takes even the veterans time, effort, and expertise to develop the procedures necessary to achieve compliance, and it takes vigilance to follow and maintain them.

If you’d like some assistance navigating your way through 21 CFR Part 111 compliance, please visit us at www.polarisconsultants.com.

by Laurie Meehan 

with Special Thanks to Rosanne Sylvia-Heeter, Director of GMP Compliance

This article appears in “Quality Lifeline”, a MasterControl publication.  http://www.mastercontrol.com/dietary_supplements/sops-dietary-supplement-distributor.html?source=n3w5quality|70130000000XEpx

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Yes, SOPs Are Hard To Write…It’s Not Just You

Ask anyone who works in a regulated industry about the purpose of SOPs and you’ll be told it has to do with minimizing variation.  Consistency, they’ll say, promotes quality.  It follows, then, that SOPs must be straight-forward and unambiguous.  If procedures are too complex or can be interpreted in a number of ways, they will not produce consistent results, and quality of the end product, whatever it is, will be at risk.  Simple.  Obvious.  SOPs 101.

It’s too bad for us that tasks are not always simple or obvious.  Often, a worker can achieve a quality result only by correctly responding to a number of variables that could arise.  An SOP that outlines such procedures has to describe each situation the worker might encounter and then provide the appropriate corresponding response.  In complicated procedures, these situations can become nested.  (Is it A, B, or C?  If it’s C, is it X, Y, or Z?)  An otherwise simple, linear set of instructions can quickly become a complex decision tree.  Also, the distinction between situations that require different responses may not be clear cut, and may only be a matter of degree.  Unless decision criteria are thoroughly explained, each worker will devise his or her own, and consistency will be lost.  Naturally, the more complicated the instructions, the more subject to misinterpretation they are.  SOP writers are challenged to capture all this complexity in a clear, concise set of procedures.

We expect a lot from our SOPs.  In many companies, SOPs don’t just supplement training, they are training.  Once upon a time, new employees were mentored by seasoned workers who would teach them the rationales behind the procedures and share undocumented nuances that they’d learned over the years.  Now, with mentorship programs becoming an extravagance most companies can no longer afford, we increasingly rely on SOPs to communicate that accumulated wisdom.  We also use SOPs to demonstrate regulatory compliance.  Sometimes, we even expect to use our SOPs as a means of legal defense, should our conduct be called into question.  Is it any surprise that the more we try to cram into our SOPs, and the more masters we have them serve, the harder it is for us to write them in a concise, easy-to-follow manner?

Smaller companies, with minimal or non-existent training staff, may rely more heavily on SOPs than their larger counterparts do, yet maintaining SOPs requires a significant resource commitment of its own.  Subject matter experts are needed to research the latest regulations, determine their impact on existing procedures, and author updates.  It’s difficult for experts in small companies to move steadily through this process because SOP maintenance is necessarily put on the back burner when profit-generating work demands. 

So, if all along you’ve been wondering why writing and revising your set of SOPs seems so hard or takes so long, maybe you can take some comfort from the fact that it’s not just you!

By Laurie Meehan

If you think you might like some help writing or maintaining your SOPs, contact us at info@polarisconsultants.com and we’ll set up some time to talk.

What SOPs Do You Need As A Dietary Supplement Distributor?

If you look at the cGMP regulations for Dietary Supplements, you’ll notice that only 1 subpart includes the words “holding” or “distributing” in its title.  With only 10 or so individual requirements, the aptly-named Subpart M, “Holding and Distributing,” is shorter than most.  If you’re thinking this means there’s a much lighter regulatory burden placed on companies that simply hold or distribute Dietary Supplements than on companies that manufacture them, you’d be right.  At the same time, it’s incorrect to assume that regulations for holding and distributing Dietary Supplements are restricted to this single subpart.  At least 8 of the 16 subparts that comprise 21 CFR Part 111 are applicable to holders and distributors.

Subpart M requires that product be held in a manner that prevents its contamination and deterioration, and preserves its purity, strength, and composition.  Subpart M may require it, but Subparts B, C, and D provide the detailed regulations your facilities, equipment, and personnel need to follow to comply with it.  To start, your warehouse has to be clean and pest-free.  Dirt, insects, lubricants, or other agents could compromise the packaging or prevent labels from adhering.  Your facility also needs proper drainage, ventilation, adequate space, and work lighting.  (Is there sufficient airflow around products that are stored on upper warehouse levels?  Do cramped or dark conditions increase the likelihood of dangerous product mix-ups?)  You must also make sure that the product you hold is not exposed to more heat, cold, humidity, or light than the manufacturer recommends.  (Is the heat tunnel you use for sealing shrink wrap too hot?  Do you have backup refrigeration?  Do you need moisture sensors?  Have all the machines you use to maintain environmental conditions been cleaned, serviced, inspected, and calibrated.  When and by whom?)   Finally, your employees have to be trained in warehouse operations and hygienic practices, and they have to be qualified for the positions they hold.  And naturally, this training needs to be documented.

Because you cannot ensure the quality of the product you distribute without verifying the quality of the product you receive, distributors must institute some of the Quality Control measures identified in Subparts E and F.  Incoming shipments must be checked against invoices and other paperwork, and applicable certificates of analysis must be verified.  Product must be inspected for damage, and the procedures for storage and handling of damaged product must be documented and followed.

Even after your product has been delivered, your regulatory obligations have not been fully discharged.  Subpart N outlines requirements you must follow when product is returned to you.  Subpart O outlines your investigative and documentation responsibilities for any product complaints you may receive.  Finally, as a distributor, you would likely play a key role in any product recall.  Subpart P enumerates the records you must keep to respond appropriately to a recall, as well as demonstrate Part 111 compliance in general.

Perhaps to those involved in pharmaceutical manufacturing or clinical research, the regulatory burden placed on holders and distributors of Dietary Supplements may seem light.  In fairness, comparatively, it is light.   But that doesn’t mean complying with all the necessary Part 111 provisions is easy or straight forward.  It takes even the veterans time, effort, and expertise to achieve compliance, and it takes vigilance to maintain it.

We at Polaris hope you find this information helpful.  Contact us at info@polarisconsultants.com with a question or post a comment.

by Laurie Meehan

This blog discusses trends and issues in the pharmaceutical and dietary supplement industries.  Click the SIGN UP link to subscribe to occasional notifications of new blog posts.