Monday, August 19, 2019

Clinical Trial Tips: Practical and Actionable

Over the years, attendees of MAGI Clinical Research Conferences have collected a set of practical, actionable suggestions for improving clinical trials. More than eighty such tips appear in the July 2019 edition of Journal of Clinical Research Best Practices*.  In this post, Polaris auditors weigh in on some of their favorite MAGI suggestions. Surprising no one, they also were eager to share some of their own.

Our Favorites Tips from MAGI

So how does a clinical trial tip earn a spot on our exalted Faves List?  First, it must be something we don’t see too often, or not as much as we’d like.(If most organizations already do a useful thing, it doesn’t really qualify as a helpful tip; it’s really just a common practice.) Second, the effort to implement the tip can’t be too onerous. If a practice requires too much interdepartmental coordination, change management, training, money, or resources, it’s not a tip. It’s a full-blown initiative.

So here they are. Each tip from MAGI attendees is in bold font. Our accompanying commentary is in plain text:
  • To help ensure quality study conduct, clinical sites should prepare protocol-specific quality checklists for each study. We’ve written about quality checklists from the auditing perspective before. They’re not a panacea, certainly, but that doesn’t mean they can’t be very useful.

  • After study close-out, sponsors and CROs should consider holding conference calls with groups of sites to capture lessons learned. This in turn could be used to improve training, SOPs, SIVs, etc.

  • As a recruitment aid, clinical sites should create pocket-sized, laminated study cards that list the inclusion/exclusion criteria for a study.  Site staff members can keep these cards in their lab coat pockets and quickly refer to them when treating a patient who could be a potential subject.

  • CROs should share risk assessments and mitigation plans with Sponsors. We agree, but would also encourage CROs to keep the sites involved and aware of risks so they can anticipate them and proceed accordingly.

  • Sponsors/CROs should ensure proper qualifications of vendors prior to executing contracts. It’s hard to argue with this logic, but we don’t see it as much as we should. Too often qualification audits come after the paperwork has been signed. Should the audit uncover noncompliance or quality risks at the vendor site, it’s much harder to get the vendor to make necessary changes after the contract is in place.

  • CROs should align 3rd party contracts with the Sponsor/CRO contract and the Clinical Trial Agreement. Yep.

Additional Tips from Polaris QA/Compliance Auditors

The MAGI list of clinical trial tips brought others to mind that we wanted to share. We applied the same criteria to these suggestions as we did to the MAGI contributions: (1) not necessarily rare, but not as common as it could be, and (2) not overly complex or expensive to implement.
  • When evaluating outsourcing partners and clinical sites, Sponsors and CROs should make sure to look at personnel turnover rates. Frequent turnovers may suggest underlying problems that could jeopardize study conduct and quality.

  • Sponsors and CROs should make sure their Monitoring Report templates are consistent with the Clinical Monitoring Plan (CMP). For example:

    • The CMP calls for a focus on a particular set of critical variables, but the report template only has a place for recording that 100% SDV was completed. This means that there’s no way to document that the monitor put special emphasis on anything.
    • The CMP requires bi-direction review of study data – a confirmation that what is in the CRF can be verified in the source, and all pertinent data in the source can be found in the CRF – but the report template only allows for the former to be documented.

  • Every member of the site team has valuable input. It’s important to include the study PI, CRC, pharmacist, and other key personnel in the discussions. In 2017, we wrote an article about the important, yet often overlooked, input that the pharmacist on site can provide.

  • There are many reasons that trial participants leave a study, many of which can’t be remedied with improved site practices. But sites that demonstrate they value the participation of their study volunteers, and honor the time they’re spending and contribution they’re making, tend to have better retention results. To that end:

    • To help participants schedule their time, sites can prepare calendars that include all study visit dates and indicate the activities and procedures they entail. (This, of course, needs to be approved by the IRB).
    • When participants arrive, they shouldn’t have to sit in a waiting room or empty exam room; they should be seen immediately so they don’t feel their time is being wasted.
    • Sites can provide beverages and light snacks to their study participants who especially appreciate them immediately after a fasting blood draw (protocol permitting, naturally). It’s a small courtesy, and not difficult to do. Whose day isn’t brightened by a proffered nosh?**
Uh oh. Now we got you all thinking about mini muffins and cheddar popcorn. Go ahead. Grab a treat. We'll talk later.

 * Journal of Clinical Research Best Practices, July 2019

** Proffered Nosh™ would be a really great name for a restaurant. Or a fictional Scotland Yard Inspector -- legendary for his wit, brilliance, wine pairings, and fashion sense.

Monday, June 10, 2019

Getting The Most From Your GMP Supplier Audit

Guest Blogger: Greg Weilersbacher
Founder & President, Eastlake Quality Consulting

All companies outsource. It’s a humbling fact that you simply can’t do it all yourself. This often has to do with resource allocation; your company may allocate dollars to build and sustain some activities in-house while choosing to contract higher-cost operations to qualified suppliers who already have the expertise and equipment. 

You may outsource the manufacturing of tablets, sterile injectable, or topical dosage form, or the GMP release and stability testing of your product. Once the production and testing is complete, the product may need to be stored under controlled temperature and humidity conditions and then distributed to locations around the globe. The Contract Development and Management Organizations (CDMOs) who execute these critical operations are of paramount importance to your company’s success. Choosing the right suppliers will also help to minimize stress-induced headaches throughout your organization. Here are the top five ways to get the most out of a supplier audit.

Monday, March 11, 2019

When Sites, eSystems, and Inspections Meet

Q: Do study site personnel need to be able to answer questions about sponsor-provided computer systems during an inspection?

A: Yes, and there’s a simple thing that sponsors and CROs can do to prepare their sites.

This excerpt was lifted from an online, interactive course entitled “Developing a Part 11 Compliance Plan in Clinical Research.” While the course mainly targeted sponsors and CROs, who have the heaviest regulatory burden in this area, sites also have Part 11 and validation concerns, as demonstrated by this question.

Presenter Lisa Olson, a CSV/Part 11 expert with Polaris Compliance Consultants, briefly described her recommendation, which is both simple and effective. (And since that is total catnip to a compliance blogger, I interviewed her after her presentation to develop the following piece.)

So here it is. Here’s what she said...

Sunday, December 9, 2018

FDA Puts Santa on the Naughty List!



December 1, 2018

Mr. Kris Kringle, Owner
Santa’s Workshop, LLC
1225 Santa Clause Way
North Pole, Arctic Circle
Dear Mr. Kringle:

The U.S. FDA inspected your manufacturing facility, Santa’s Workshop, LLC at
1225 Santa Claus Way, North Pole Arctic Circle, from April 2 to April 20, 2018.

This warning letter summarizes significant violations of CGMP regulations for finished product. See 21 CFR, parts 210 and 211. During our inspection, our investigators observed specific violations including, but not limited to, the following.

CGMP Violations

1.    Your firm failed to ensure that each person engaged in the manufacture, processing, packing, or holding of product has the education, training, and experience, or any combination thereof, to enable that person to perform his or her assigned functions (21 CFR 211.25(a) and 211.28).

Many members of your Enterprise Labor Force (ELF) unit lacked sufficient prior experience for designing and assembling (b)(4). At the time of our inspection, no ELF members had received training on CGMPs, and most were unaware of their responsibilities in the areas of cleanliness and proper attire. Hands and faces were often coated with chocolate, and bells on hats and shoes prevented protective apparel from attaining a proper fit. More generally, factory staff demonstrated an undisciplined, almost gleeful disregard for quality procedures. On three separate occasions, at critical stages of the manufacturing process, floor workers erupted into spontaneous song and dance.

Monday, October 15, 2018

The One-Hour Study Site Audit

In an effort to tease out the priorities of a clinical study site audit, I asked six of our most experienced GCP auditors the following question:

If you only had one hour to conduct a study site audit,
what would you look at?

[Obligatory warnings:  Do not try this at home. This is just a simulation. Caveat lectorem. Dinosaurs in the mirror are bigger than they appear. Et cetera.]

Of course it’s not possible to conduct any kind of meaningful audit in so short a time, but it’s an interesting thought exercise because it gets to the heart of study site risk.

Monday, August 13, 2018

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.

Tuesday, July 10, 2018

Hackin' the GDPR

Trying to comply with the GDPR got you down?
Maybe our parody will cheer you up.

(Sung to the tune of Lennon-McCartney's "Back in the U.S.S.R.")