Interpretation of E.U. Annex 13 Survey

Part 1 of 2

Purpose of Survey - This survey is intended to gain an industry wide perspective on the interpretations of Annex 13 and how they have been applied in practice. A firm's interpretation of the guidance will impact clinical trial supply operations. By participating in this survey you will be able to benchmark your application of the guidance against others and possibly gain insights into alternative interpretations that will enable you to optimize your operation while maintaining compliance.

Confidentiality Statement - This survey is being conducted by Drug Development Resources, Inc. (DDR), a Cambridge, Massachusetts based consulting firm for the sole purpose of understanding the breadth of interpretations of Annex 13 across the industry. The data obtained will be analyzed and distributed to all participants by DDR. Participant firm names will not be revealed at any time. If you would like to participate but require additional confidential non disclosure measures, please contact Jerry Boudreault, President at 781 589 8985.

Time - We estimate that the survey will take approximately 15-20 minutes to complete.

All individual responses will be held confidential, only aggregate results will be reported.

Thank you in advance for your participation!

Annex 13 Text -

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Optional Contact Information (*required)

First Name

Last Name

Title

Company

Phone

Email*

Department

General Company Info

1.	How many employees at your firm?

	<25
	25-50
	50-100
	100-200
	200-500
	500-1000
	>1000
	Other:

2.	Does your firm have an E.U. base of operation?

	Yes, E.U. subsidiary
	Yes, E.U. partner
	Yes, E.U. virtual office
	No (Skip to Q. 4)
	Yes, Other:

3.	If you answered yes to question 2, in which country(ies) is (are) your E.U. office(s) located?

4.	Does your firm use E.U. CROs to manage E.U. clinical trials?

	Yes
	No (Skip to Q. 7)

5.	If you answered yes to question 4, which CROs do you use?

6.	Does the CRO provide compliance services?

	(Select all that apply.)
	No
	Importation services
	QP Services
	Legal Entity
	Other:

7.	How many E.U. clinical trials are you currently conducting?

8.	How many E.U. clinical trials have you initiated since May 2004?

9.	For trials approved prior to May 2004, what impact did implementation of the clinical trial directive and Annex 13 have?

	(Select all that apply.)
	None
	Change in Investigational Medicinal Product (IMP) labeling
	Clinical Trial Application (CTA)
	Other:

10.	Has an Clinical Trial Application (CTA) of yours not been accepted or required follow-up action due to labeling?

	Yes
	No (Skip to Q. 12)

11.	If you answered yes to question 10, what was the issue that was the cause of rejection?

IMP Importation and Release

12.	Where is (are) your drug substance(s) manufactured?

	U.S.
	E.U.
	Other:

13.	Where is your drug product manufactured?

	U.S.
	E.U.
	Other:

14.	Where do you perform final packaging of the Investigational Medicinal Product (IMP)?

	U.S.
	E.U.
	Other:

15.	Who holds the manufacturing authorization that enables import of the Investigational Medicinal Product (IMP) for E.U. use?

	E.U. Drug Product CMO
	E.U. Clinical Packaging/Distribution CMO
	Contract QP
	E.U. CRO
	U.S. sponsor
	E.U. office of sponsor
	Partner
	Other:

16.	Do you have a technical/quality agreement that defines detailed roles and responsibilities between sponsor and manufacturing authorization holder?

	Yes
	No

17.	What country is your port of entry into the E.U.?

18.	If you import drug product into the E.U., what release testing is performed on Investigational Medicinal Product (IMP) upon receipt in the E.U.?

	None
	ID only
	Full Retest
	Other:

19.	What documentation does the QP require to perform the E.U. release?

	(Select all that apply.)
	Completed drug product batch record
	Certificate of analysis for drug product
	Certificate of compliance for drug product
	Completed drug substance batch record
	Certificate of analysis for drug substance
	Certificate of compliance for drug substance
	Documentation of proper shipping conditions
	Other:

20.	What evidence of GMP compliance did your firm as sponsor provide to the manufacturing authorization holder?

	(Select all that apply.)
	QP onsite audit of your facility and systems
	Quality Systems Questionnaire
	FOIA EIR Reports
	Other:

21.	Did the country of import's regulatory authority perform a site inspection?

	Yes
	No
	No, but expressed intent to do so some time in the future

22.	Do you outsource drug product manufacturing for E.U. Investigational Medicinal Product (IMP)?

	Yes
	No (Skip to Q. 24)

23.	If outsourcing to a U.S. CMO and then importing into the E.U., what evidence of GMP compliance did your U.S. based CMO provide to the manufacturing authorization holder?

	(Select all that apply.)
	QP onsite audit of their facility and systems
	Sponsor audit report
	FOIA EIR Reports
	Quality Systems Questionnaire
	Other:

24.	Do you maintain a Product Specification File (PSF) with the manufacturing authorization holder listed in your Clinical Trial Application (CTA)?

	Yes
	No (Skip to Q. 26)
	Don't Know (Skip to Q. 26)

25.	If you answered yes to question 24, what form does the Product Specification File (PSF) take?

	They are formal, separately prepared documents with a discrete reference number (e.g. a process description or description of testing)
	They are less formal, comprised of a collection of information (i.e. batch records for production, packaging & labeling, methods, testing, etc.)

26.	Do you have written procedures that describe the process for keeping the Product Specification File (PSF) up to date and communicating changes to the QP?

	Yes
	No
	Don't Know

General Labeling Requirements

27.	Who is the final authority on E.U. labeling requirements at your firm?

	CRO
	CMO
	Sponsor Regulatory Affairs
	Sponsor Clinical Operations
	Sponsor Supply Operations
	No set responsibility - it changes all the time
	Other or combo:

28.	Which of the following would most closely describe your approach to label copy development?

	We have adopted standardized labeling that is adjusted to the needs of specific studies when necessary. The standards are included in a written procedure.
	Label requirements are recreated for each new study. Design is recreated from scratch.
	Depends on the person approving

29.	Who performs translation of label text?

	General translation service
	Specialty translation service dedicated to pharmaceuticals
	CRO
	Internal personnel
	Other:

30.	Do you require a back translation of the labeling and if yes, who performs the back translation service?

	General translation service
	Specialty translation service dedicated to pharmaceuticals
	CRO
	Internal personnel
	Do not require back translation
	Other:

31.	Where do you obtain information about country specific labeling requirements?

	Consult Regulatory Affairs Department
	Central Database
	Subscription to a service for that purpose
	CRO
	Other:

32.	Do you use Interactive Voice Response Systems (IVRS)?

	Yes
	No (Skip to Q. 35)

33.	If IVRS is used, do you justify the absence of label information required by Annex 13 because the information is provided by the IVRS? (e.g. the elimination of a subject number because the pharmacist contacts the IVRS and is given instructions.)

	Yes
	No (Skip to Q. 35)

34.	If the answer to question 32 is yes, which information do you justify not supplying on the label?

35.	Do you interpret the Annex 13 requirements differently for in-hospital or in-clinic use products versus those which will be taken home by the patient?

	Yes
	No (Skip to Q. 37)

36.	If you answered Yes to question 35 what is different - explain your logic.

37.	Do you provide directions for use separate from the primary and secondary package labeling?

	Yes
	No (Skip to Q. 39)

38.	If you answered Yes to question 37, do the directions for use provide information prescribed by Annex 13 that is not included on either the primary or secondary label?

	Yes
	No

39.	Which of the following approaches to identifying a Lot number field would be acceptable to your firm?

	(Select all that apply.)
	Batch
	Batch No.
	Lot No.
	LOT
	All of the Above
	None of the Above
	Other:

40.

Just in time labeling (JIT labeling) is a means to add an additional label to the Investigational Medicinal Product (IMP) at time of shipment to provide additional information required by the destination site, but not all sites in the study. To illustrate, suppose there is a requirement in Sweden to include investigator name on the IMP. For orders shipping to Sweden that additional information would be supplied at time of shipment. For orders to other destinations the standard label would be acceptable and a JIT label would not be applied. Do you use JIT labeling?

	Yes
	No (Skip to Q. 42)

41.	If you answered Yes to question 41, what information prescribed by Annex 13 that is not included on either the primary or secondary package labeling is included in the directions for use?

42.	Which of the following does your firm use to communicate shelf life on the label?

	(Select all that apply.)
	Expiry
	Expiry Date
	Expiration Date
	Retest Date
	Use by Date
	None - we use a document other than the label
	Other:

43.	If you answered None to question 42, what document is used to communicate shelf life?

44.	If you answered Retest Date in question 42, how do you update the label if new information becomes available?

	(Select all that apply.)
	Unshipped product is over labeled by CMO
	We don't over label product that has been shipped
	We provide labels to the site - they over label
	We provide labels to the CRO or monitor - they over label

45.	If you answered Retest Date in Question 42, have you had any push back from regulatory authorities on the use of this term?

	Yes
	No (Skip to Q. 47)

46.	If you answered Yes to Question 45, please explain what push back you have received.

47.	How do you communicate refrigerated storage temperature on the label?

	Store between 2-8 � C
	Keep Refrigerated
	Other:

48.	How do you communicate frozen storage temperature on the label?

	Store between -10 to -25 � C
	Keep Frozen
	Other:

49.	How do you communicate controlled room temperature on the label?

	Store between 20 to 25 �C
	Store at Room Temperature
	Store at controlled room temperature
	Store in a cool dry place
	Other:

50.	What sponsor ADDRESS information appears on the PRIMARY label?

	(Select all that apply.)
	US Sponsor
	EU office of US Sponsor
	Investigator
	CRO
	None

51.	What sponsor PHONE number appears on the PRIMARY label?

	(Select all that apply.)
	U.S. Sponsor
	E.U. Office of U.S. Sponsor
	Investigator
	CRO
	Centralized call in center
	None