LOGFILE No. 17/2011 - December 2011





During October 2011 there have been a number of developments in the regulation of the pharmaceutical industry. In October all reported issues have come from the EU and USA regulatory authorities.


  • New Medicrime Convention to be launched in Russia
  • Pharmeuropa online
  • Technical guide for the elaboration of monographs – 6th edition
  • Handling of duplicate marketing authorization submissions
  • Guide to control and monitoring of storage and transportation temperature conditions for medicinal products and active substances.
  • IMB, Customs and Gardai in global INTERPOL operation


  • New transparency report outlines proposals for enforcement data
  • Inspectional observation summaries
  • Q&A about pathogenic agent contamination of animal-derived drug ingredients
  • Guidance for Industry Incorporation of PhysicalChemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting
  • Guidance for Industry- Warnings and Precautions, Contraindications, and Boxed Warning Sections of Labeling Content and Format
  • Draft Guidance on Media Fills for Validation of Aseptic Preparations for Positron Emission Tomography Drugs


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Council of Europe

New Medicrime Convention to be launched in Russia

The Council of Europe, the Russian Ministry of Public Health and Social Development and the Federal Service on Surveillance in Healthcare and Social Development are looking to give a boost to the fight against counterfeit medical products and similar crimes. To this end a new Medicrime Convention will be opened for signature at a conference in Moscow on 26 to 28 October Click on press release for further detail


Pharmeuropa online

In order to publish Pharmeuropa articles and draft texts for comment as early as possible and on an on-going basis, Pharmeuropa will be a 100% online format starting with Pharmeuropa 24.1. Current subscribers to the paper version can still access the old electronic version Everyone can access the new and free online version. The new homepage gives news and information, the familiar articles published in Pharmeuropa and provides access to 3 databases:

  • Texts for Comment
  • Bio & Scientific Notes
  • Pharmeuropa Archives

Find out more and register as a user by clicking on: pharmeuropa

Technical guide for the elaboration of monographs – 6th edition

This document is a guidance for the authors of monographs and also a means of communicating to the users of the European Pharmacopoeia, especially industry, licensing authorities and official medicines control laboratories, the principles for the elaboration of monographs. Since the principles applied and guidance given for the elaboration of monographs should be the same as those applied by licensing authorities, the Technical Guide may also serve as a guideline in the elaboration of specifications intended for inclusion in licensing applications.It is necessary to bear in mind that a monograph will be a mandatory standard and must be applicable in licensing procedures in all Member States of the Convention on the Elaboration of a European Pharmacopoeia. The procedures for the tests and assays in the individual monographs must therefore have been validated according to the current practice at the time of their elaboration.To access the guide click on: elaboration of monographs


Handling of duplicate marketing authorization submissions

The European Commission has published this document update as it has noticed that requests for duplicate marketing authorisations under Article 82(1) of Regulation (EC) No 726/2004 have increased steadily and this is a trend that is likely to continue in the future as the use of the centralised procedure rises.

A marketing authorisation granted under Regulation 726/2004 empowers the holder to market the medicinal product in the entire EU. the Regulation limits the ability of applicants/holders to obtain more than one marketing authorisation per medicinal product

In particular, Article 82(1) of Directive Regulation 726/2004 provides that

"Only one authorisation may be granted to an applicant for a specific medicinal product.

However, the Commission shall authorise the same applicant to submit more than one application to the Agency for that medicinal product when there are objective verifiable reasons relating to public health regarding the availability of medicinal products to health-care professionals and/or patients, or for co-marketing reasons."

This document provides examples of applications that fall under the scope of Article 82(1). For further information click on: duplicate MA applications

Irish Medicines Board (IMB)

Guide to control and monitoring of storage and transportation temperature conditions for medicinal products and active substances.

IMB has published this guidance to provide guidance to human and veterinary medicinal product manufacturers, wholesalers and transporters of human medicinal products in Ireland and manufacturers of active pharmaceutical ingredients (APIs) in relation to conditions for cold storage/cold-chain and controlled temperature storage.

For many medicinal products, storage and transportation temperatures are a highly significant factor in maintaining the quality of medicinal products throughout the distribution network. The distribution chain is seldom simple and distribution systems can vary enormously. In its simplest form, the chain involves shipment direct from the manufacturer to the customer or end user but, in reality, the chain is rarely this short. In its more complex form, the distribution chain may involve a number of storage and transit locations, including airports, docks, and a variety of methods of transport, including aircraft.

To view a copy of the guidance click on: transportation guide

IMB, Customs and Gardai in global INTERPOL operation.

The Irish Medicines Board (IMB), Revenue‟s Customs Service and An Garda Síochána have announced details of their role in Operation Pangea IV which is an international week of action targeting the online sale of counterfeit and illegal medicines in the interests of protecting public health. They were among authorities from more than 80 countries who participated in this INTERPOL co-ordinated initiative which took place from 20 to 27 September 2011. This is the fourth Operation PANGEA to-date focusing on websites that supply illegal and dangerous medicines. The initiative is the largest internet–based action of its kind in support of the International Medical Products Anti-Counterfeiting Taskforce (IMPACT). In Ireland, the joint operation by the IMB, Customs and Gardaí led to the detention of 51,621 tablets, capsules and creams with an estimated value in excess of €150,000. The number of packages detained during the operation in Ireland by Customs was 492. The substances detained included products for weight loss and erectile dysfunction as well as mood stabilisers.

Under Operation PANGEA IV, national medicines agencies, police and customs with support from Internet Service Providers (ISPs), electronic payment industry and delivery services worked together to target the three main components abused in the illegal website trade: the Internet Service Provider (ISP), electronic payment system and the delivery service.

Click on PANGEA to view the IMB press release

United States of America

The US Food and Drug Administration (USFDA)

New transparency report outlines proposals for enforcement data

The U.S Food and Drug Administration has released 8 new draft proposals in a report titled “Food and Drug Administration Transparency Initiative: Draft Proposals for Public Comment to Increase Transparency By Promoting Greater Access to the Agency‟s Compliance and Enforcement Data.”

These draft proposals are focused on making FDA‟s compliance and enforcement data more accessible and user-friendly, and they are part of FDA‟s ongoing efforts to increase the transparency of FDA‟s operations and decision-making.The draft proposals are open for public comment via the dockets procedure until Dec 2 2011.

Click on press release for further information

The 8 draft proposals are :

1: FDA should explore different ways to improve data quality and facilitate more timely data disclosure by expediting data entry, expediting inspection review and classification, and/or updating the data more frequently. Tools to improve data quality and speed data disclosure may include, for example, providing new technologies to investigators, introducing other process improvements, and/or implementing administrative incentives. To implement these types of tools effectively, FDA also should explore how frequently data should be updated in order for it to be useful to stakeholders.

2: Although FDA‟s inspections database webpage currently provides an e-mail address where stakeholders can submit questions about the database, FDA should explore whether:

  • reporting buttons, or other tools specifically focused on error reporting, would allow stakeholders to more easily identify potential errors in compliance and enforcement data, and
  • the Agency can implement procedures for investigating potential errors and correcting data, when appropriate, that would enable the Agency to remedy the errors more expeditiously.

3: FDA should explore how to present its compliance and enforcement data graphically and better utilize mobile web applications to draw more users to its compliance and enforcement webpages, and to encourage data analysis.

4: FDA should explore whether it can better integrate its compliance and enforcement data, as well as its other publicly available data on regulated firms, to make the data more user-friendly and easier to analyze.

5: FDA should explore whether additional, or more specific search criteria (e.g., criteria that would enable individual product-specific or violation-specific searches), or more sophisticated search capability (e.g., predictive name searches) would make the inspections database more user-friendly and the data easier to analyze.

6: FDA should explore whether posting additional data compilations or analysis, such as the Agency‟s most common inspections observations or the warning letter compilations, both of which it already posts, would increase transparency or better inform the Agency‟s own compliance efforts

7: FDA should explore ways to better utilize social media, such as Facebook and Twitter, as well as Agency-sponsored webinars and automatic e-mail notifications, to better communicate with the public regarding its compliance and enforcement efforts.

8: FDA should provide appropriate context for the compliance and enforcement data that it discloses, to help ensure that the data is not misinterpreted or misused.

Full detail plus previous proposals can be viewed by clicking on: transparency initiative

Inspectional observation summaries

Readers have probably heard FDA inspectors talk of using Turbo EIR and even if they haven‟t, they may well have experienced it. Take a look at the wording on company Form 483‟s etc and compare the wording with FDA‟s Inspectional observation summaries which can be viewed on inspection observations

You can also use this continually updated listing to see what are FDA‟s “most unwanted” ie its top 10 inspectional observations for whichever part of the industry most concerns you. Click on: most cited and select your section of the industry to reveal all.

Q&A about pathogenic agent contamination of animal-derived drug ingredients

FDA has published new Q&A‟s about the risks, preventive measures and means of minimizing contamination of animal-derived drug ingredients. These Q&A‟s cover:

  • What are FDA‟s primary concerns about pathogenic agent contamination of animal-derived drug ingredients?
  • What manufacturing contamination risks are presented by the different pathogenic agents?
  • What are some ways to minimize pathogenic agent contamination in incoming animal-derived raw material?
  • Are there control measures for minimizing pathogenic agent contamination in animal-derived drug ingredient manufacturing facilities?

To view the recent Q&A‟s / guidance click on Q&A's and read items 7-10 inclusive.

Guidance for Industry Incorporation of Physical Chemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting

Pharmaceutical manufacturers aiming to thwart drug product counterfeiting have been investigating readily available technologies that may make drug products more difficult to duplicate. One approach that pharmaceutical manufacturers appear to be considering involves adding a trace amount of an inactive ingredient(s) to an existing section of the dosage form. A unique physical-chemical characteristic of that ingredient makes it possible to detect and authenticate legitimate dosage forms, and to identify counterfeits.

Examples of substances that may be incorporated into SODFs as PCIDs include inks, pigments, flavors, and molecular taggants. Such PCIDs may allow product authentication by their presence alone or may be used to code the product identity into or onto the SODF

This document is intended to provide guidance to pharmaceutical manufacturers who want to use physical-chemical identifiers (PCIDs) in solid oral dosage forms (SODFs). A PCID is a substance or combination of substances possessing a unique physical or chemical property that unequivocally identifies and authenticates a drug product or dosage form. This guidance provides recommendations to pharmaceutical manufacturers on

  • design considerations for incorporating PCIDS into SODFs,
  • supporting documentation to be submitted in new drug applications (NDAs) and abbreviated new drug applications (ANDAs) to address the proposed incorporation of PCIDs in SODFs,
  • supporting documentation to be submitted in post approval submissions to report or request approval to incorporate PCIDs into SODFs,
  • and procedures for reporting or requesting approval to incorporate PCIDs into SODFs as a post approval change.

The incorporation of components or features used in radiofrequency identification for drug products is outside the scope of this guidance. In addition, this guidance does not apply to manufacturing or formulation changes, made in conjunction with the addition of a PCID, that go beyond simply inserting the PCID into a blending or mixing operation (e.g., adding a PCID to a non-functional tablet film coating is covered by this guidance, but adding a non-functional film coating that contains a PCID to a previously uncoated tablet involves manufacturing changes that are not covered by this guidance). The incorporation of a PCID into the packaging or labeling is not covered in this guidance.

To view the guidance in full, click on: indentifiers guidance

Guidance for Industry- Warnings and Precautions, Contraindications, and Boxed Warning Sections of Labeling Content and Format

This guidance is intended to assist applicants and reviewers in drafting the WARNINGS AND BOXED WARNING sections of labeling, as described in the final rule amending the requirements for the content and format of labeling for human prescription drug and biological products (21 CFR 201.56 and 201.57)

This guidance provides recommendations on the following:

  • How to decide which adverse reactions or other potential safety hazards are significant enough to warrant inclusion in the warnings and precautions, what information to include when describing those adverse reactions; and how to organize the warnings and precautions section
  • What situations warrant a contraindication; what information to provide in those situations when the use of the product is contraindicated; and how to organize the contraindications section.
  • When to include a boxed warning; and what information to include in the boxed warning section

To view the guidance click on: labeling guidance

Draft Guidance on Media Fills for Validation of Aseptic Preparations for Positron Emission Tomography Drugs

Recognizing that many PET drug producers are unfamiliar with the drug approval process, FDA issued the guidance PET Drug Applications – Content and Format for NDAs and ANDAs, and held a public meeting in March 2011 to assist applicants in preparing NDAs and ANDAs for the three most commonly used PET drugs. In comments to the guidance and in questions raised at the public meeting, stakeholders requested that FDA provide guidance on media fills for validation of aseptic preparation for PET drugs. This guidance is being issued in response to these requests and is designed to help manufacturers of PET drugs comply with FDA regulations.

Click on announcement and / or media fill guidance for further detail


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gmp-review news

gmp-review news is compiled and edited by Malcolm Holmes e-mail: malcolmbrian.holmes@tiscali.co.uk

This information service is also published as a Monthly Regulatory Update on The Pharmaceutical and Healthcare Sciences Society website http://www.phss.co.uk ©The Pharmaceutical and Healthcare Sciences Society 2011