Use of PDF File Format 1.7 (PDF Version 1.7) for Regulatory esubmissions

PDF (Portable Document Format) as a preferred format for regulatory esubmission in the pharmaceutical and biotechnology industry. Since 1999, the Adobe Acrobat Portable Document Format (PDF) is the building block of regulatory electronic submissions. All regulatory agencies those who are accepting PDF documents they have very strict requirements for the format and setting within PDF files.

Regulatory Agencies including FDA, and EMA published PDF Specification guidance. According to the guidance PDF files should be in File Format 1.4 (PDF version 1.4). Pharmaceutical and Biotechnological industry following the same and they are submitting there documents in PDF 1.4v to Regulatory agencies.

Recently ICH ESTRI (The International Conference on Harmonisation Electronic Standards for the Transfer of Regulatory Information) they have answered the question related to use of PDF version 1.7 documents for esubmissions they are recommending pharmaceutical industry and Regulatory agencies (Regional Authorities) to use PDF version 1.7 documents for regulatory submissions.

FDA Thoughts about use of PDF File Format 1.7

According to FDA esubmission team Currently FDA CDER accepting PDF 1.7 version documents However FDA working with PDF specifications they will be updating their PDF Specification document over the summer to reflect this change to PDF 1.7v, but the change is in fact active now. If sponsor will receive any validation error for using 1.7v PDF they can ignore the error. FDA we will not reject any esubmission based on PDF version of the document.

EMA Thoughts about use of PDF File Format 1.7

There is no any information about use of PDF version 1.7 from EMA. Even in the new EU Validation Criteria version 3.1 document (EU Validation Criteria version 3.0 will be effect from 1st Sep 2011) says PDF documents should be in 1.4v only.

However the EU Module 1 specification guidance being updated and will be published 31st of August 2011. It will clarify the use PDF v1.7 documents.

Swissmdic Thoughts about use of PDF File Format 1.7

According to Swissmedic eSubmission team the current Swiss eCTD validation criteria v1.1 and the Guidance for Industry on Providing Regulatory Information in eCTD Format v1.2 require PDF v1.4 documents, Swissmedic will not apply more tight restrictions than EU does in this respect. Therefore Swissmedic will accept PDF v1.7 as well and will change its requirements accordingly. Swissmedic will implement the same requirements as the EU has, which are based on

• The new EU validation criteria v3.1 to be implemented by EU on September 1, 2011
• The ICH Q&A document v1.20 dated June 16, 2011
• The ESTRI file format recommendation dated April 5, 2011

According to the current Swiss eCTD validation criteria v1.1 and the Guidance for Industry on Providing Regulatory Information in eCTD Format v1.2, the use of PDF v1.7 is not allowed and, as the validation engines still validate based on this, the use of PDF v1.7 will be apparent as B5 error during technical validation. As Swissmedic will now accept PDF v1.7 in spite of the current requirements, Swissmedic will expect sponsors to explicitly declare the use of PDF v1.7 documents by using the form 'FO Technical Validation'.

Health Canada Thoughts about use of PDF File Format 1.7

According to Health Canada guidance document, Guidance for Industry: Preparation of Drug Submissions in Electronic Common Technical Document (eCTD) Format, technical requirements for eCTD submissions can be found in section 4.1- file formats. It states the following:

The following components should be provided in both PDF (Adobe Acrobat, version 5.0, 6.0, or 7.0) and word-processed format:

• PM;
• Quality Overall Summary (QOS);
• Certified Product Information Document (CPID);
• Comprehensive Summary: Bioequivalence (CS:BE); and
• Responses to SDNs, Clarifaxes, NONs, and NODs.

Health Canada will accept higher version of PDF documents, Sponsor can use PDF v1.7 documents for Health Canada esubmissions.

Features of PDF version 1.7

The PDF 1.7 specification includes all of the functionality previously documented in the Adobe PDF Specifications for versions 1.0 through 1.6. The PDF 1.7 was approved by ISO Technical Committee 171 in January 2008 and published as ISO 32000-1:2008 on July 1, 2008. ISO 32000-1:2008 is the first ISO standard for the full function PDF.

In the PDF version1.7 new features includes increased presentation of 3D artwork; XFA 2.4 rich text elements and attributes; multiple file attachments (portable collections); document requirements for a PDF consumer application; new string types: PDFDocEncoded string, ASCII string, byte string; PKCS#7 with SHA384, SHA512 and RIPEMD160.