PSDGLIST Archives

April 2017

PSDGLIST@LISTS.MICROBIOLOGYNETWORK.COM

Options: Use Monospaced Font
Show Text Part by Default
Condense Mail Headers

Message: [<< First] [< Prev] [Next >] [Last >>]
Topic: [<< First] [< Prev] [Next >] [Last >>]
Author: [<< First] [< Prev] [Next >] [Last >>]

Print Reply
Sender:
Pharmaceutical Stability Discussion Group <[log in to unmask]>
Date:
Mon, 17 Apr 2017 22:14:01 +0000
Reply-To:
Pharmaceutical Stability Discussion Group <[log in to unmask]>
Message-ID:
Subject:
MIME-Version:
1.0
Content-Type:
text/plain; charset="utf-8"
In-Reply-To:
Content-Transfer-Encoding:
base64
From:
Michael Barron <[log in to unmask]>
Parts/Attachments:
text/plain (1 lines)
Hi Emil, et.al.,

I was hoping for someone to comment on my intended humor about wine storage coolers…at least one person got a chuckle and replied off-line.  Thank you!
In the spirit of continuing education in stability matters and being informed consumers, I offer the following.

Whether the label statement ‘Do Not Refrigerate’ is more about the functionality of the auto-injector or about the solution stability, I assert that storage in a “Cool” place is already implicitly permitted by Mylan, USP, and FDA.   See below for rationale (italics and highlights are mine for emphasis).


USP General Chapters: <659> PACKAGING AND STORAGE REQUIREMENTS

An article for which storage at Controlled room temperature is directed may, alternatively, be stored and shipped in a cool place or refrigerated, unless otherwise specified in the individual monograph or on the label.


The EpiPen package insert states
“Store at 20° to 25°C (68° to 77°F);
excursions permitted to 15°C-30°C
(59°F-86°F) (See USP Controlled Room
Temperature). Do not refrigerate. Protect
from light. Contains no latex.”



Note that “Cool” (9C-14C) is not “otherwise specified”.

·         By not being specified, cool storage of the product, by default,  is acceptable.

·         Makes sense…would the manufacturer suspect harm in cool storage and not place the warning on the label/package insert?

·         Both label and package insert need FDA approval…they have the stability data, would they let that get through if suspect?



This seems straight forward to me…does anyone see it differently?





*********************************

Continuing thoughts and considerations…for the hard core.

Cool storage alone does not guarantee an extended product life within specifications…but there are some indicators that can.  Here’s one:

·         The Federal Shelf Life Extension Program (SLEP) run by FDA and DoD finds that many drugs can be extended well beyond their expiration dates if stored well.  If you don’t know about this program it would make for interesting reading.  SLEP https://www.ncbi.nlm.nih.gov/pubmed/16721796

·         I couldn’t find EpiPen in the SLEP specifically because I don’t have the full database but you can see that three other auto-injectors in the program were all extended by 2X to 3X the original shelf life…i.e. between 9 and 18 years!  https://en.wikipedia.org/wiki/Shelf_Life_Extension_Program.  Click on the Archive Copy in Wiki page.



Therefore, regarding EpiPen, it seems there are two main questions:

1.       Does Cool storage extend the shelf-life of the drug and if so, by how much?

a.       The USP Monograph for Epinephrine Injection gives a clue:

§  Labeling—The label indicates that the Injection is not to be used if its color is pinkish or darker than slightly yellow or if it contains a precipitate.

·         There is real value in Appearance testing, especially to a trained eye.

§  In fact, all USP epinephrine solution monographs, whether for injection, nasal, or bronchial inhalation, only bear the warning of protect from light.  Not one mentions protect from refrigeration.

·         EpiPen does not have a monograph but I believe the solution for injection is the same

2.       Cool storage may not inhibit injector functionality, whereas Cold storage might.

a.       Do the springs and other parts wear out in two years without use?

                                                               i.      The answer is…I don’t know but it seems possibly not…see SLEP comments above.

·         This assuming the SLEP tests included auto-injector functionality.

                                                             ii.      Would EpiPen device be far inferior after 25 years on the market and a couple of rounds of improvements?  Does not seem likely…but I don’t know.


b.      Does cooling the device limit its ability to “recover” normal functionality once it warms up again to room temperature?

                                                               i.      I don’t have much on that other than Meridian Medical Technologies (part of King-Pfizer legacy), maker of AtroPen and, as far as I know, the CMO for Mylan’s EpiPen, has a warning only for Do Not Freeze.  So it is possible for at least one style of auto-injector to be refrigerated.

                                                             ii.      …but that does not mean the auto-injector for EpiPen is similar.





Now…if only someone from Mylan could weigh-in with the real story…you know, someone who doesn’t need their job anymore. ☺



These comments represent my own thinking and do not necessarily represent my employer, colleagues, friends, or perhaps anyone. ☺

Thanks for listening fellow Stabilitarians!



All the best,

Michael Barron

Quality Chemical Laboratories



PS: Tony - I’ve known you since the early years of PSDG in the early 90’s so it is with this familiarity and fondness I offer the following.  Since you are a responsible adult (hopefully with a wine cooler at your house for medicinal purposes ☺), have you considered carrying a prefilled syringe instead?  It’s a lot cheaper, with a longer shelf-life…plus it looks like you can refrigerate it.





-----Original Message-----
From: Pharmaceutical Stability Discussion Group [mailto:[log in to unmask]] On Behalf Of Emil Friedman
Sent: Thursday, April 13, 2017 10:29 PM
To: [log in to unmask]
Subject: Re: [PSDGLIST] EpiPen Stability



Contact the manufacturer.  13C might or might not drop it below some sort of temperature at which something drops out of solution .  Consider what might happen out in the boonies if your EpiPen fails to work properly.  But don't hold your breath (pun intended); they may have data showing the 5C is bad but may not have tested it at 13C.  Stability studies are expensive to do.



-------------------------------------------

Emil M Friedman, PhD

880 Salem Ave

Hillside, NJ 07205

732-227-5942 (land line at work)

216-287-0821 (cell)

908-355-8319 (home phone number)

[log in to unmask]<mailto:[log in to unmask]>

[log in to unmask]<mailto:[log in to unmask]>

http://www.statisticalconsulting.org



On Mon, Apr 3, 2017 at 7:31 AM, Michael Barron < [log in to unmask]<mailto:[log in to unmask]>> wrote:



> Hi Tony,

>

> Not familiar specifically with EpiPen stability but assuming the 5C

> label warning is based on scientific evidence I would start with using

> a wine cooler.  Designed for operating @ ~13C.  Everyone has

> one...right? :)

>

> A quick message from my phone.

> Thanks,

> Michael

> ________________________________________

> From: Pharmaceutical Stability Discussion Group [[log in to unmask]

> MICROBIOLOGYNETWORK.COM] on behalf of Tony Cundell

> [[log in to unmask]]

> Sent: Saturday, April 01, 2017 1:59 PM

> To: [log in to unmask]<mailto:[log in to unmask]>

> Subject: [PSDGLIST] EpiPen Stability

>

> I carry an EpiPen when hiking or visiting botanical gardens as I am

> highly allergic to bee stings.

>

> With the short expiration dating of EpiPens I have to replace them

> annually.Their cost have gone through the roof!

>

> Although the product labeling warns against refrigeration could I

> refrigerated the device when not needed and put it in my hiking bag

> when hiking. With this strategy I might extent the shelf life to 2 or 3 years.

>

> Any comments

> --

> Tony Cundell, Ph. D.

> Consulting Microbiologist

> Email: [log in to unmask]<mailto:[log in to unmask]>

> Phone: 914 725-3947

> Cell: 914 841-0074

>

> =================================

> The nature of this service is to provide a medium for communication.

> The specific statements and endorsements of individuals participating

> in the discussions are not necessarily those of The Microbiology

> Network, Inc., the PSDG, or the sponsors of the list.

>

> ------------------

> The PSDGList (http://microbiol.org/psdglist.htm) is operated from The

> Microbiology Network (http://www.microbiol.org) and supported by our

> sponsors as a service to the scientific community.   Please take a second

> to visit our sponsors' web sites and say thank you for their support

> of this service.

>

>

> Avista Pharma Solutions - http://www.avistapharma.com/

>    Comprehensive testing and CMC services organization

>    Analytical and Microbiology support to early stage API and drug

> product development and manufacturing.

>

>

> BahnsonEnvironmental Specialties - http://www.eschambers.com/

>    Manufacturer of Quality Stability Chambers, Warm & Cold Rooms,

> Freezers and

>    Ultra Low Storage Chambers with Complete Validation, Maintenance &

> Calibration

>

> Cincinnati Sub-Zero - http://www.cszindustrial.com/

>     Provides a large selection of environmental chambers from

> benchtop, reach in to walk-in

>     rooms along with chambers for freeze/thaw, temperature cycling

> applications.

>

> =================================

> The nature of this service is to provide a medium for communication.

> The specific statements and endorsements of individuals participating

> in the discussions are not necessarily those of The Microbiology

> Network, Inc., the PSDG, or the sponsors of the list.

>

> ------------------

> The PSDGList (http://microbiol.org/psdglist.htm) is operated from The

> Microbiology Network (http://www.microbiol.org) and supported by our

> sponsors as a service to the scientific community.   Please take a second

> to visit our sponsors' web sites and say thank you for their support

> of this service.

>

>

> Avista Pharma Solutions - http://www.avistapharma.com/

>    Comprehensive testing and CMC services organization

>    Analytical and Microbiology support to early stage API and drug

> product development and manufacturing.

>

>

> BahnsonEnvironmental Specialties - http://www.eschambers.com/

>    Manufacturer of Quality Stability Chambers, Warm & Cold Rooms,

> Freezers and

>    Ultra Low Storage Chambers with Complete Validation, Maintenance &

> Calibration

>

> Cincinnati Sub-Zero - http://www.cszindustrial.com/

>     Provides a large selection of environmental chambers from

> benchtop, reach in to walk-in

>     rooms along with chambers for freeze/thaw, temperature cycling

> applications.

>



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

The nature of this service is to provide a medium for communication.  The specific statements and endorsements of individuals participating in the discussions are not necessarily those of The Microbiology Network, Inc., the PSDG, or the sponsors of the list.



------------------

The PSDGList (http://microbiol.org/psdglist.htm) is operated from The Microbiology Network (http://www.microbiol.org) and supported by our sponsors as a service to the scientific community.   Please take a second to visit our sponsors' web sites and say thank you for their support of this service.





Avista Pharma Solutions - http://www.avistapharma.com/

   Comprehensive testing and CMC services organization

   Analytical and Microbiology support to early stage API and drug product development and manufacturing.





BahnsonEnvironmental Specialties - http://www.eschambers.com/

   Manufacturer of Quality Stability Chambers, Warm & Cold Rooms, Freezers and

   Ultra Low Storage Chambers with Complete Validation, Maintenance & Calibration



Cincinnati Sub-Zero - http://www.cszindustrial.com/

    Provides a large selection of environmental chambers from benchtop, reach in to walk-in

    rooms along with chambers for freeze/thaw, temperature cycling applications.

=================================
The nature of this service is to provide a medium for communication.  The specific statements and endorsements of individuals participating in the discussions are not necessarily those of The Microbiology Network, Inc., the PSDG, or the sponsors of the list.

------------------
The PSDGList (http://microbiol.org/psdglist.htm) is operated from The Microbiology Network (http://www.microbiol.org) and supported by our sponsors as a service to the scientific community.   Please take a second to visit our sponsors' web sites and say thank you for their support of this service.


Avista Pharma Solutions - http://www.avistapharma.com/
   Comprehensive testing and CMC services organization
   Analytical and Microbiology support to early stage API and drug product development and manufacturing.


BahnsonEnvironmental Specialties - http://www.eschambers.com/
   Manufacturer of Quality Stability Chambers, Warm & Cold Rooms, Freezers and
   Ultra Low Storage Chambers with Complete Validation, Maintenance & Calibration

Cincinnati Sub-Zero - http://www.cszindustrial.com/
    Provides a large selection of environmental chambers from benchtop, reach in to walk-in
    rooms along with chambers for freeze/thaw, temperature cycling applications.

ATOM RSS1 RSS2