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  • 1.  Preclinical vs. Nonclinical

    This message was posted by a user wishing to remain anonymous
    Posted 08-Jun-2018 16:11
    This message was posted by a user wishing to remain anonymous

    Hello,

    This is a very basic question, so my apologies if it is a duplicate of any thread. 

    The question is, do preclinical and nonclinical indicate the same type of study?  For example, preclinical studies are those performed in laboratory and in animals prior to being used in a clinical setting, whereas nonclinical are the same types of studies (animal/laboratory) performed at any time during the drug development process.

    A little background: I have been approached about auditing for "Nonclinical Studies" per 21 CFR 58.  Now, my original understanding was that these "GLP" requirements were focused solely on animal study laboratories and not intended to be applied to a GMP/GCP setting.  Simply, these are solely for animal testing laboratories, even though they imply a general laboratory application (GLP).  Unfortunately I am seeing a great deal of miscommunication between industry and those hiring for positions so I am attempting to clarify this for head hunters, and so forth.  I want to make sure I am properly explaining when I am approached about these types of positions, and not confusing the issue.  My background is mostly pharmaceutical GMP/GCP auditing, though I have extensive laboratory and medical device QA experience as well.  

    Thank you!


  • 2.  RE: Preclinical vs. Nonclinical

    Posted 09-Jun-2018 10:31
    Hi Anonymous,

    Nonclinical and Preclinical are often used interchangeably. However, technically, "nonclinical" studies are those that are not clinical studies. They are not studies that are just in animals, as you state, but they may able be in other test systems. "Test system" is a Good Laboratory Practice (GLP) term that is basically the animal, microorganism, plant, etc. that you are testing the test article on. Nonclinical studies are discussed in the GLPs.

    "Preclinical studies" are the same as nonclinical, but are done (technically) prior to performing clinical trials.

    If these are headhunters looking for GLP Consultants, I find it distressing that they are looking for someone who has no GLP experience. One cannot simply take a GMP or GCP auditor, for example, and have them do a GLP audit without proper training. There are so many facets to the GLPs that one needs to learn before performing an audit. GLPs are not black and white. One cannot simply read the regulations and claim that they are familiar with the GLPs. There are so many shades of gray that the GLP Auditor must know. These are accomplished by education, training and experience... as is stated in the GLPs. Most of the GLP auditors that I know regularly attend the Society of Quality Assurance (SQA) meetings where we have direct access to the FDA regulators and Inspectors. Many of the FDA personnel also give talks or open mic sessions which yield a wealth of knowledge and current thinking for the GLP professionals.

    As to your comment about GLPs not applying to a GMP or GCP setting, that is not quite accurate, as more of these labs are claiming that they are GLP, so it would apply to them. And here's why I state that. For GMP labs: At the last SQA meeting, we were reminded that if the test article is not prepared according to GLPs, we have to take an exception to the GLPs in our reports (we knew this part already).  The FDA is cracking down on the Study Director just accepting a C of A as proof of the identity, strength, purity, composition, etc. of the test article. They want to see that the Study Director has seen the data supporting this, and other aspects of the test article manufacturing. Therefore, as a reaction to this. more and more GMP labs are  asking for GLP training, and incorporating GLP aspects in their lab. I just trained GMP personnel at a lab a couple of weeks ago, and am routinely getting requests for GLP training from GMP labs. For the GCP aspect... the analysis of bioanalytical samples from human trials are being conducted according to GLPs in many labs. Otherwise for human GCPs, that's all I see. However, for the FDA's CVM studies for animal pharmaceuticals, devices, etc., GLP studies are routinely conducted, and I get many requests for GLP audits of this sort.

    Also, the FDA 21CFR 58 is more than just a "requirement". They are a regulation, a law, and must be followed in the USA.

    I hope that this helps answer your question.


    Best regards,

    Robin

    Robin Guy, MS, DABT, RQAP-GLP
    Robin Guy Consulting, LLC
    Toxicology and GLP Consulting
    Lake Forest, IL, USA
    robinguy@robinguy.com
    1.847.295.9250

    ========================




  • 3.  RE: Preclinical vs. Nonclinical

    Posted 11-Jun-2018 06:03
    Hello,

    Just wanted to reiterate what Robin said is that they are often used interchangeably, and also different countries use one over the other was well ... even though they are asking for the same thing.  She is also correct that from a pure technical point of view: nonclinical means those type of testing that encompass a large part of development such as electrical testing, mechanical testing, fatigue testing, individual component testing.  Whereas, preclinical does indicate something done prior to clinical trials such as animal testing, First In Person (FIP - or FIM as First in Man not being politically sensitive), or usability studies.  Often those companies that are not required to do clinical studies - everything can be done on the "bench" - would be doing nonclinical testing, but as Robin mentioned I see these terms mixed alot, even within the same document.

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    Richard Vincins RAC
    Vice President Regulatory Affairs
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  • 4.  RE: Preclinical vs. Nonclinical

    Posted 11-Jun-2018 07:43
    Your characterization and understanding of pre-clinical versus non-clinical is exactly the same as mine. Pre-clinical implies IND-enabling studies and I've tried to switch to use the term non-clinical applying all through product development.
    About auditing and 21 CFR 58: auditing is not part of the normal course of activities for GLP-compliant studies. The QA Unit monitors laboratory work during a study and reviews the final report and raw data to ensure accuracy and completeness in the reported data, and the latter is a type of audit though it is not usually called that in my experience. The GLP testing facility probably has an audit program for laboratory operations compliance with SOPs.
    Like you, I've seen improper use of the term and uses of GLP in relationship to GMP/GCP.
    Best of luck to you.
    Lee

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    Lee McDonald
    Westfield NJ
    United States
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  • 5.  RE: Preclinical vs. Nonclinical

    Posted 12-Jun-2018 20:49

    Hi Lee,

    I beg to differ with you. The QAU definitely audits studies, and they are routinely called "audits". In the 1978 preambles, Comment 92 has a statement about the "internal quality assurance audits" (although earlier it said that the FDA prefers the term "inspections"). The 1987 GLP Preambles also are very clear in that regard. They state that the QAU "is responsible for detecting any such deviations by its inspection and audit procedures". In addition, Sponsors routinely send their QA to audit Contract Research Organizations (CROs) before the study starts (mostly as a Qualification audit), during the study, and/or after the report has been audited by the CRO's QAU (audited draft report). As a matter of fact, a client and I just tried to get an audit scheduled for a large CRO and they are so booked up with audits, they cannot accommodate us until September.  At the SQA meetings, the term "audit" is normally used for GLP inspections that are conducted by a QAU.

    Best regards,

    Robin

    Robin Guy, MS, DABT, RQAP-GLP 
    Robin Guy Consulting, LLC 
    Toxicology and GLP Consulting
    Lake Forest, IL, USA



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    Robin Guy MS
    Toxicology and GLP Consultant
    Lake Forest IL
    United States
    robinguy@robinguy.com
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  • 6.  RE: Preclinical vs. Nonclinical

    Posted 13-Jun-2018 07:55
    So good to hear Robin chime in here.  I certainly did many many QA audits of pre-clinical studies when I was RA/QA Director of large animal surgical facility (2006-2008).  We were a contract in-life test lab. Auditing is definitely required under 21 CFR 58 and by OECD Guidance. 

    We also audited key partners and suppliers such as Marshfield Lab's diagnostic testing and their controls, pathology labs, calibration houses, sample and record storage facilities, etc. We had our own specific QAU SOPs for this, as required. FDA audits GLP labs and they specifically look at the effectiveness of the QAU during the audit.

    And yes, I was a member of SQA and attended training at the SQA annual meetings and IACUC training through private companies.

    QAU is very integratedin GLP Studies, from protocol through to final reports,  and  system/facility infrastructure development and maintenance.


    Ginger Cantor, MBA, RAC
    Founder/Principal Consultant
    Centaur Consulting LLC centaurconsultingllc@gmail.com
    (+1) 715 - 307-1850