PILLBOX+FAQ

=PILLBOX Q&A [Answers from Discussions on June 1 and June 8, 2011]= =Link to Federal Register notice on [|PILLBOX]= Pillbox is a publicly accessible online repository of digital images and descriptive information for solid oral dosage form medications. This project seeks to promote utilization of the SPLIMAGE element of the Food and Drug Administration (FDA) Structured Product Label (SPL) through development and use of imaging standards and methodologies. With this notice, NLM seeks to evaluate the photography methodology and procedures it has developed for standardized high-resolution images of solid oral dosage form medications that are appropriate for inclusion in the SPL. Participating organizations will be invited to submit samples of their solid oral dosage form medications to NLM for imaging with the resulting image files provided to participants, who may choose to voluntarily include them in their subsequent SPL submissions to FDA. Image files that are voluntarily submitted to FDA as part of an SPL listing submission will be included in the publicly accessible, production version of Pillbox. This initiative is an important element of ongoing efforts to enhance patient safety, reduce adverse drug events, and improve the quality and availability of drug information….

High-Level Process:

> a. Firm’s name and address. b. Name, e-mail address, and telephone number of the person submitting the medications. > c. Name, e-mail address, and telephone number of the person who is responsible for receiving the final images of the medications. > Update (Jan 2012):
 * 1) Let NIH know that your company intends to participate in this program. Send e-mail to // pillbox@mail.nih.gov. //
 * 2) Select and ship samples. Send the smallest volume stock package(s) totaling at least 8–10 representative solid oral dosage form medications of the same drug product. Include the accompanying prescribing information.
 * 3) Provide contact information for the person(s) submitting the solid oral dosage form medications and receiving the final images.
 * 1) Send the representative solid oral dosage form medications to: NLM PILLBOX IMAGING PROJECT, Attn: Staff Pharmacist, 2094 Gaither Rd., Suite 240, Room 245, Rockville, MD 20850.
 * ** PILLBOX Update [D Hale, S Phillips, W. Hess] **
 * Over part of 2011, there had been an impasse on getting images created
 * Photography has started and is on a fast track by HPCC. We want to get the original sets of samples imaged and back to the manufacturers for review.
 * Have partnered with another group at NLM to get these images created according to the specifications
 * Products submitted by firms have been transferred to a pharmacy near another NLM worksite.
 * David and his group’s role in the __imaging__ is minimal right now. His role now is to facilitate this discussion.
 * Action(s) for [Q: //same procedures for destruction of samples?] – need to gather a list of questions to make sure everything is being done in compliance with the regulations and the Federal Register notice.//
 * David’s director (Dr. Steve Phillips) would like to have a discussion with stakeholder groups – anxious to get feedback on the images and to plan
 * FDB perspective: have been taking images and supplying them for a long time. They’d be interested in seeing some early images – to provide feedback from a pharmacy dispensing perspective.
 * Some modifications have been made to the previous standard – those will be under review soon. Some of the issues raised before may be back as issues now.

Questions:
 * 1) Will there be a different location to ship samples? FDA is going to be meeting with NLM representatives next week.
 * 2) Procedure for destruction/permanent disposal of the project?FDA is going to be meeting with NLM representatives next week.
 * 3) Should people not be shipping samples at this point?If things haven’t been shipped yet, consider waiting a week or two.
 * 4) What if the contact information for receipt of images has changed? Who do we contact?FDA is going to be meeting with NLM representatives next week.
 * 5) Technical questions related to the images – contact HPCC (point of contact to be provided in the near future)
 * 6) Do you have an idea when images will be available for review?Planning to be available sometime this month.
 * 7) What was the purpose of the other project? NLM often collects a lot of information for databases (research projects).

[01-June-2011]

Question:
Have you gotten any samples yet?

Answer:
//Yes - 2 sets of samples [as of June 8, 2011]//

Reference(s) :
//(Include link to authoritative source(s) when available)//

[01-June-2011]

Question:
How many companies have indicated that they are planning to send samples (so far)?

Answer:
//4 companies have expressed interest so far [as of June 8, 2011]//

Reference(s) :
//(Include link to authoritative source(s) when available)//

[01-June-2011]

Subject:
controlled substance, DEA, schedule I, II, III, IV, V

Question:
Can you accept controlled substance samples?

Answer:
Yes. If you are planning to send controlled substances, contact //pillbox@mail.nih.gov //to obtain the relevant license information needed for the shipping of these products//.// You can also contact this email address for additional DEA and other information.

Reference(s) :
From the Federal Register Notice: //NLM, in collaboration with FDA, has set up a photography laboratory at an FDA facility in Rockville, Maryland for the purpose of generating standardized images of representative solid oral dosage form medications for the duration of this project. This facility is registered with the Drug Enforcement Administration.//

[01-June-2011]

Subject:
taking photographs

Question:
Have you started taking photographs yet?

Answer:
Not yet. As soon as the Federal Register Notice was published, we were able to start the process of reactivating the laboratory and contract. This process is now underway.

Reference(s) :
//(Include link to authoritative source(s) when available)//

[01-June-2011]

Subject:
photos from sponsors

Question:
Can I take my own photographs and send them in the SPL file?

Answer:
Currently that is outside the scope of the Federal Register Notice. If this is something that you wish to explore further, you may want to contact the FDA at spl@fda.hhs.gov to discuss further.

Reference(s) :
//(Include link to authoritative source(s) when available)//

[01-June-2011]

Question:
Will your methodology for taking these photos be made public?

Answer:
Yes. The methodology will be made public.

Reference(s) :
// From the Federal Register Notice: ... NLM, working with FDA, has developed a standardized methodology for creating digital images of solid oral dosage form medications//

[01-June-2011]

Subject:
turn-around time, turnaround time, processing time

Question:
How long will it take to get images back from NLM?

Answer:
The turnaround time is based on resources and volume of images received. A sustained level of participation from sponsors & the number of available photographers will contribute to reduction of turn-around time.

Reference(s) :
//(Include link to authoritative source(s) when available)//

[01-June-2011]

Subject:
image specification

Question:
What will the image look like?

Answer:
Right now, the specification is very simple. The image will be presented on a 18% gray background, with obverse and reverse displays for a tablet, and two rotations that allow the markings on the capsule to be displayed for a capsule. There is still discussion on whether to include a ‘fiduciary’ (a ruler or measurement presented as part of the image file.

Issue of ‘fiduciaries’ (rulers or measurements on the image) – The image is a data element of the product. The ruler on the image has become a topic of discussion – as to whether that is an inclusion of a data element. Main concern is that that data is included in the listing information, and the image is supposed to be free of data elements from the SPL. Should it be part of the image? We want the image to be viewed in terms of the SPL. The images are easier to look at without the rulers (nothing gets in the way of the image of the solid oral dosage). Also, when you scale the photo with the ruler present, if you scale up or down, the ruler can be distorted. //As of June 8: the discussions are leaning towards either (1) not providing a ruler, or (2) a representation of size using dots - WITHOUT making measurements..//

Reference(s) :
//(Include link to authoritative source(s) when available)//

[01-June-2011]

Question:
How many files will we get back for each sample?

Answer:
For each sample, ideally we’d like to send two files: an uncompressed, color-corrected image of a rather large size - 10MB PNG file, and a JPG rendition of the master image of less than 150K size for use in the SPL. The National Library of Medicine would like firms to validate the master image and then verify that the JPG is a accurate representation of the larger file. The JPG will be attached to the SPL. Once the SPL is posted to DailyMed NLM will validate the image against the master file and retain the master file in PNG format for their master list.

Reference(s) :
From the Federal Register Notice: //In order to test the imaging methodology in an operational setting// //and to begin developing a production version of Pillbox, NLM is offering, on a time-limited basis, to provide manufacturers, including repackagers, and private label distributors who send product samples to NLM, image files suitable for inclusion with their SPL files that are being submitted to FDA.//

[01-June-2011]

Question:
What is the format of the larger size file?

Answer:
The larger image format will be an uncompressed file of PNG format (Portable Network Graphic), with color space intact.

Reference(s) :
[01-June-2011]

Subject:
(Subject Text - this level is optional but requested)

Question:
When will the FDA start accepting these image files?

Answer:
This is a question for the FDA.

Reference(s) :
//(Include link to authoritative source(s) when available)//

[01-June-2011]

Subject:
(Subject Text - this level is optional but requested)

Question:
When will information about inclusion of the image file in the SPL be added to the Implementation Guide?

Answer:
//It's already in the implementation guide:// []

   //  //  //  // </// characteristic > // </// subjectOf > //

Reference(s) :
[] ( SPL Implementation Guide for FDA Drug Establishment Registration and Drug Listing v2.0) in section //3.1.11. Product characteristics (pg 15)//

[01-June-2011]

Subject:
Test file failure

Question:
I tried a test file with an associated image against the test validator. Why did I get this error?

<span style="font-family: 'Calibri','sans-serif';">I inserted code according to the implementation guide, and included a test file image (splimage.jpg). I’ve included the files zipped. Change the extension to ‘zip’ to open it. <span style="font-family: 'Calibri','sans-serif';">I tried it twice against pragmatics validator with different image names. Both times, I received this error:
 * <span style="font-family: 'Calibri','sans-serif'; font-size: 13px;">Overview of Errors **
 * 1) <span style="font-family: 'Calibri','sans-serif'; font-size: 13px;">[|Image file obtained from FDA must have the file name assigned by FDA.]
 * <span style="font-family: 'Calibri','sans-serif'; font-size: 13px;">What's happening? **

Answer:
<span style="color: blue; font-family: 'Arial','sans-serif'; font-size: 13px;">The image associated with the SPLIMAGE field has to have a file name assigned by NLM/FDA.

Reference(s) :
//(Include link to authoritative source(s) when available)//

[01-June-2011]

Question:
Is the submission of the image file required by the FDA? Will the submission of the image file be required by the FDA in the future?

Answer:
<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">This is a question for the FDA. Currently, inclusion of these image files is voluntary.

<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">Opinions from other groups: The NLM sees the value in having these images available for public efficacy and to improve the efficacy of this initiative. Downstream compendia producers, such as FirstDataBank and Medispan, also have expressed strong interest in having access to product image files.

Reference(s) :
From the Federal Register Notice: //Participating organizations will be invited to submit samples of their solid oral dosage form medications to NLM for imaging. Resulting image files will be provided to participants, who may choose to voluntarily include them in their subsequent SPL submissions to FDA. Image files that are voluntarily submitted to FDA as part of an SPL listing submission will be included in// // the publicly accessible, production version of Pillbox. //

[01-June-2011]

Subject:
(Subject Text - this level is optional but requested)

Question:
What kind of file format will the FDA be looking for for the SPL_IMAGE?

Answer:
This is a question for the FDA. However, in the current implementation guide, section //3.1.11. Product characteristics (pg 15)// [] The xml example describing the SPLIMAGE makes reference to a JPG file:

<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;"><subjectOf> <span style="font-family: 'Calibri','sans-serif'; font-size: 15px;"><characteristic classCode="OBS"> <span style="font-family: 'Calibri','sans-serif'; font-size: 15px;"><code code="SPLIMAGE" codeSystem="2.16.840.1.113883.1.11.19255"/> <span style="font-family: 'Calibri','sans-serif'; font-size: 15px;"><value xsi:type="ED" mediaType="image/jpeg"> <span style="font-family: 'Calibri','sans-serif'; font-size: 15px;"><reference value="//file name.jpg//"/> <span style="font-family: 'Calibri','sans-serif'; font-size: 15px;"> <span style="font-family: 'Calibri','sans-serif'; font-size: 15px;"></subjectOf>

Reference(s) :
[] ( SPL Implementation Guide for FDA Drug Establishment Registration and Drug Listing v2.0) in section //3.1.11. Product characteristics (pg 15)//

[01-June-2011]

Subject:
filename, name of file, naming convention

Question:
How will the file be named?

Answer:
<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">NLM and FDA are finalizing the details of the filenames. One possibility is a 128 bit hexadecimal string (otherwise known as a GUID) unique to the image.

Reference(s) :
//(Include link to authoritative source(s) when available)//

[01-June-2011]

Question:
Are you accepting samples of over-the-counter products?

Answer:
<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">Yes, we are accepting over-the counter product samples.

Reference(s) :
From the Federal Register Notice: //Manufacturers, including repackagers, and private label distributors of prescription and over-the-counter solid oral dosage form medications may submit products for imaging.//

[01-June-2011]

Question:
Are you accepting samples of homeopathic products?

Answer:
<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">Yes, we are accepting homeopathic product samples

Reference(s) :
From the Federal Register Notice: //Manufacturers, including repackagers, and private label distributors of prescription and over-the-counter solid oral dosage form medications may submit products for imaging.//

[01-June-2011]

Question:
Are you accepting samples of veterinary products?

Answer:
<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">Yes, we are accepting veterinary samples

Reference(s) :
From the Federal Register Notice: //Manufacturers, including repackagers, and private label distributors of prescription and over-the-counter solid oral dosage form medications may submit products for imaging.//

[01-Jun-2011]

Subject:
pill sample

Question:
<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">Why do you need more than 1 of each sample?

Answer:
<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">We want to make sure we get the most aesthetically pleasing example - as the pictures are taken the images will show the granularity of the product, therefore displaying irregularities.

Reference(s) :
From the Federal Register Notice: //Select and ship the smallest volume stock package(s) totaling at least 8–10 representative solid oral dosage form medications (e.g., tablets, capsules) of the same drug product. In order to ensure the safety of facility staff and compliance with appropriate federal// //regulations please include the accompanying prescribing information.//

[01-Jun-2011]

Subject:
(Subject Text - this level is optional but requested)

Question:
Can I provide unpackaged samples, such as quality lots?

Answer:
National Library of Medicine requests that you send small volume stock packaging and not yet expired. It was suggested to send the smallest unit of product that would contain the USPI to reduce FDA interactions, but provided the handlers at the labs with basic product and handling information for safety reasons.

Reference(s) :
From the Federal Register Notice:
 * //The expiration date on the submitted products’ packaging should be the longest available expiration date.…//
 * //Select and ship the smallest volume stock package(s) totaling at least 8–10 representative solid oral dosage form medications (e.g., tablets, capsules) of the same drug product. In order to ensure the safety of facility staff and compliance with appropriate federal regulations please include the accompanying prescribing information.//

[01-Jun-2011]

Subject:
(Subject Text - this level is optional but requested)

Question:
<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">Who would provide the samples?

Answer:
<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">If the manufacturer wants to receive product images for use in the SPL, the manufacturer is responsible for providing the samples. Currently, this is a voluntary initiative.

Reference(s) :
<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">From the Federal Register Notice: //Manufacturers, including repackagers, and private label distributors of prescription and over-the-counter solid oral dosage form medications may submit products//

[01-Jun-2011]

Subject:
(Subject Text - this level is optional but requested)

Question:
<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">Do we need to resubmit a new photograph every year?

Answer:
This is a question for the FDA. Currently, inclusion of these image files is voluntary. This is currently a volunteer effort; companies are not required to submit SPLIMAGE files at this time. Sponsors are encouraged to keep the photographs included in the SPL up-to-date by obtaining new image files when a product is added or its oral dosage form characteristics have changed.

Reference(s) :
[01-Jun-2011]

Subject:
(Subject Text - this level is optional but requested)

Question:
<span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">Are you thinking of posting the names of the companies involved in the process? <span style="font-family: 'Calibri','sans-serif'; font-size: 15px;">Are you thinking of including a list of the products provided by each of the companies?

Answer:
Yes. The Pillbox website will publish the names of firms intending to participate.

Reference(s) :
From the Federal Register Notice: //Manufacturers, including repackagers, and private label distributors who participate in this process will be acknowledged on the Pillbox Web site and in other communications about the project//

[01-Jun-2011]

Subject:
(Subject Text - this level is optional but requested)

Question:
Could images be provided for ‘drugs for further processing’ – would images help for Imports?

Answer:
Currently, inclusion of these image files is voluntary. Companies are not required to submit SPLIMAGE files for any document type at this time. Additionally, that type of submission that is outside the scope of the Federal Register Notice. If this is something that you wish to explore further, you may want to contact the FDA at spl@fda.hhs.gov to discuss further