Thursday, October 23, 2014
2010 Index Minimize

Report
Number

Description

Category

Date
Issued

158
Rx-360 Summary of Revisions to Chapter 7 of the EU GMP Guide

Regulation 15-Dec-10
153
Rx-360 Summary of International API Inspection Program

 
Regulation 05-Dec-10
 142
Rx-360 Summary of US FDA - Strategic Priorities 2011 – 2015

Data
Sharing
26-Oct-10
137
Chinese State Food and Drug Administration Proposed Route of Registration for APIs, Excipients and Auxiliary Materials

 
Legislation 12-Oct-10
135
Regulators are collaborating and sharing more information than ever before

 
Data Sharing 08-Oct-10
134
New MHRA Guidance on Inactive API Suppliers
Guidance 07-Oct-10
 132
Read the Rx-360 Summary of U.S. Legislation HR 759, the Drug Globalization Act
Legislation 04-Oct-10
109
Rx-360 Summary of Proposed U.S. Legislation S3690, Drug Safety and 
Accountability Act of 2010
Legislation 11-Aug-10
108
Rx-360 Summary of Proposed U.S. Legislation HR4678 Foreign Manufacturers Legal Accountability Act of 2010 
Legislation 10-Aug-10
105

 

 


Rx-360 Summary of Proposed US Legislation HR 5740 is now available
Legislation 05-Aug-10
98
Rx-360 Summary of the UPS Pain in the Supply Chain Survey
Survey 14-Jul-10
97
Rx-360 Summary of U.S. FDA's Draft CMC Guidance Document

Guidance

13-Jul-10

96


Rx-360 Summary of U.S. FDA's Transparency Initiative

Guidance

13-Jul-10

93
Rx-360 Summary of the U.S. China Economic and Security Review Commission Biopharma Report
 

Data Sharing

29-Jun-10

83
Rx-360 Summary of EC Directive 2001/83/EC to Prevent Falsified Medicine
 

Guidance

7-Jun-10

82


From Brazil ANVISA Issues New GMPs with Rx-360 Summary

Guidance

 

 

4-Jun-10

75


U.S. FDA Urges Industry to Take Steps to Prevent Cargo Theft

Guidance

28-Apr-10

73
Rx-360 Summary of US Congressional Hearing - Drug Safety an Update from FDA

Legislative

1-Apr-10

72
Rx-360 Summary of the U.S. FDA Final Guidance on Serialization

Guidance

31-Mar-10

71


Rx-360 Summary of the WHO Guidance on Starting Materials

Guidance

29-Mar-10

61


Rx-360 Summary of EU GMPs: Explanatory Note on Preparation of Site Master Files

Guidance

24-Feb-10

58


Rx-360 Summary of Changes to the “Anti-Counterfeiting Directive” 2001/83/EC Proposal For A Directive Of The European Parliament And Of The Council
Anti-Counterfeiting Directive” 2001/83/EC

Guidance

16-Feb-10

56


Rx-360 Summary of US FDA guidance to avoid drugs shortages involving medically necessary products

Guidance

2-Feb-10

53
Rx-360 Summary to Q & A Guidance for Industry: Pharmaceutical Components at Risk for Melamine Contamination [Supplement to August 2009 Rx-360 Summary on FDA Guidance for Industry: Pharmaceutical Components at Risk for Melamine Contamination]

Guidance 27-Jan-10
52
EU Proposed GMP Changes to Chapter 1 - Quality Management System
     To view or download Chapter 1 
click here
     To view or download Rx-360 Summary of Chapter 1 
click here
Guidance 20-Jan-10
52


EU Proposed GMP Changes to Chapter Chapter 2 Personnel
  To view or download Chapter 2-  
click here
  To view or download Rx-360 Summary of Chapter 2- 
click here  

Guidance  20-Jan-10

49


Rx-360 Summary of the U.S. FDA guidance to avoid drugs shortages involving medically necessary products

Guidance

8-Jan-10

 

     

 

  

Rx-360 Summary of European Commission recently published draft revisions to both Chapters 5 and 7 of the EU GMP Guide Minimize

The European Commission recently published draft revisions to both Chapters 5 and 7 of the EU GMP Guide,  titled “Production” and “Outsourced Activities” respectively.   Revisions to both address optimization of control over the supply chain and contractors.  We will provide a summary of the Chapter 5 draft revisions in the near future.  Revisions to Chapter 7 include expansion of scope from Contract Manufacture and Analysis to Outsourced Activities, thus including many more functions than addressed in the current version.  Consistent with changes made to other Chapters and Annexes of the EU GMP Guide that have been recently revised, the concepts of Quality Systems (ICHQ10) and Risk Management (ICHQ9) have been incorporated.   Comments on the draft revisions, if companies are interested, are due February 28, 2010.
 

To view or download the EU Draft Revisions,  click here

To view or download the Rx-360 Summary, click here

  

International API Inspection Pilot Programme Minimize

On September 23, 2010 the EMA, TGA and FDA published an interim report summarizing their progress on sharing of information from GMP inspection of international API manufacturing sites.  This program began in 2008 and will end in December 2010, at which time a final report will be published.  The purpose of the program is to determine whether it is possible to leverage the inspections performed by the participating regulatory bodies and decrease the number of duplicate inspections.  By minimizing duplicate inspections it may be possible to effectively leverage inspectorate resources to perform additional inspections of other manufacturing sites. The report is positive in the results it reports from the early phase of the pilot, and we look forward to the more detailed final report. 

To view or Download the EU Document, Click Here

To View or Download Summary, Click Here

 

  

Revisions to Chapter 7 of the EU GMP Guide Minimize

A draft revision to Chapter 7 of the EU GMP Guide, Outsourced Activities, has been published by the European Commission.   Comments from interested parties are due February 28, 2011.  This chapter specifies requirements for outsourced activities associated with medicinal products.  It reflects the globalization of the supply chain and corporate relationships associated with the sourcing, manufacture, testing and distribution of human medicinal products that have occurred since the chapter was originally written.

  • The most significant change has been to expand the scope of the this chapter beyond the previous title of Contract Manufacture and Analysis to Outsourced Activities,  making it more inclusive in its scope.  This would appear to include all outsourced GMP, or GMP-related activities;
  • The principles of Quality Systems, ICHQ10, have been incorporated in this chapter consistent with the incorporation of these principles in other revised Chapters and Annexes of the EU GMP Guide
  • The principles of Risk Management, ICHQ9, have been incorporated in this chapter consistent with the incorporation of these principles in other revised Chapters and Annexes of the EU GMP Guide

To view or Download the EU Document, Click Here

  

US FDA Strategic Priorities Minimize

 US FDA - Strategic Priorities 2011 – 2015
Responding to the Public Health Challenges
of the 21st Century
Public Comment Draft (9/29/2010)

 

On September 29, 2010 FDA published a review draft of their strategic priorities for 2011 through 2015 and have solicited public comments by 1 November 2010.  This document identifies goals and areas of focus for FDA for that time period.  Four areas are identified as strategic priorities:  1) advancing regulatory science, 2)  strengthening the global supply chain,  3) strengthening compliance and enforcement to ensure protection of public health and 4) addressing special needs populations.  Their long term efforts include the need to address food safety and the safety and effectiveness of medical products.   Commissioner Hamburg continues to stress the need to improve regulatory science and its application within the review and inspection process.   In the attached Rx-360 summary we focus only on those aspects of the draft plan that address the supply chain, but readers may find it valuable to review the entire document. 

  
Download / view the  Rx-360 summary by 
clicking here

Download / view the  FDA document by clicking here

 

  

Chinese State Food and Drug Administration Proposed Route of Registration for APIs, Excipients and Auxiliary Materials Minimize

State Food and Drug Administration (SFDA) of China recently published a draft document describing their proposed route of registration of API, excipients and auxiliary material manufacture and quality assurance.  The registration route is based on their analysis of the Drug Master File (DMF) content and process used in the US and EU.  Of particular interest:

·   The drug product manufacturer is the entity responsible for the quality of component materials used in the drug

·   Scope covers drugs registered for sale in China, apparently not APIs or excipients which are made for export only

·   Clinical investigational materials are not addressed in this document

·   Audit reports from the drug product manufacturer audit of their suppliers mentioned in this document must be submitted in the filing

Download / view the Rx-360 summary by clicking here

By special arrangement IPQ is making their full
story on the proposed SFDA regulation available to
Rx-360 members. 

Click here to read the story

 

.

  

Regulators are collaborating and sharing more information than ever before Minimize

Regulators are collaborating and sharing more non-public information than ever before.  Each jurisdiction finds they must leverage their limited resources by effectively collaborating with their partners in other countries and geographic areas. We report here on two recently signed confidentiality agreements.  In both agreements, the partners have provided assurance that they can effectively protect this non-public information.   On September 15, 2010 EMA and FDA formally extended their existing confidentiality agreements for an indefinite period.  This agreement allows sharing of inspection reports and other non-public information between the agencies.  We provide the link to the EMA press release.  On September 24, 2010, FDA and ANVISA signed a confidentiality agreement that permits sharing of non-public information.  This is the first confidentiality agreement between the two regulatory agencies, and acknowledges Brazil’s rising importance as a pharmaceutical market and supplier and ANVISAs rise as a regulatory agency. 

To read the agreements between agencies click on the agreement below:

Agreement between the US FDA and ANVISA

Agreement between the US FDA and EMA

  

Rx-360 Summary of US HR 759 Drug Globalization Act Minimize

U.S. Legislation: HR 759, the Food and Drug Globalization Act

 

HR 759 was drafted and introduced last year.  Recently a refined “discussion draft” has been published. The increased globalization of the pharmaceutical manufacturing and distribution supply chains has led to a focus on ensuring safety of these items in light of the Heparin incidents of 2007 and 2008.   The most significant differences between the discussion draft and the original draft bill are the removal of food safety features, inclusion of mandatory recall authority for FDA, and inclusion of excipients.  The food safety aspects were incorporated into  HR 2749, mandatory recall authority appears to be prompted by some recent  large recalls, and excipients seem to come and go in terms of coverage under these bills.  Fundamentally, while FDA would be given greater authority under this proposed legislation, it also specifies that manufacturers are responsible for the safety of the materials which they purchase and use in their manufacturing operations. 


Download / view the entire Rx-360 summary of HR 759 click here

  Download / view HR 759 click here


 

  

U.S. Senate Proposed Legislation S.3690, Drug Safety and Accountability Act of 2010 Minimize


U.S. Senate Proposed Legislation S.3690, Drug Safety and Accountability Act of 2010

 

On August 3, 2010 Senator Michael Bennet of Colorado introduced S. 3690 - the Drug Safety and Accountability Act of 2010.   After introduction it was referred to the Committee on Health, Education, Labor and Pensions.  This bill incorporates aspects of others which were previously introduced to Congress relative to drug safety.  Primary features of this bill include:

  • Expanding the definition of “adulteration” to include those drugs that do not comply with requirements in this bill to have and implement a Quality management plan and documentation of the drug supply chain.

    1. The Quality management plan requires periodic on-site audits by the company  Further, specifications and test methods must be sufficient “…to detect any hazard that has been, or is reasonably likely to be, present in or on the drugs during production, manufacturing, processing, packing, holding or transporting.” 
    2.  
      The supply chain documentation “…shall show that the drug and the ingredients of the drug were manufactured, prepared, propagated, compounded, processed, and handled in a manner ensuring the identity, safety, quality, purity and strength of such drug.”  The supply chain documentation is to include “…names, addresses, phone numbers and GPS coordinates of each producer, manufacturer, distributor and shipper involved in the production of a drug or the production or transport of the active ingredients of a drug…”.
       
  • FDA is to develop and maintain information systems that are capable of identifying and tracking drugs and their active ingredients.  FDA has one year after this bill is enacted to develop such systems.

  • FDA is not to consider whether products are OTC drugs in their decisions regarding timing and frequency of inspections

  • FDA is to pursue Mutual Recognition Agreements and report on progress to Congress

  •  FDA is to have mandatory recall authority (similar to H.R. 5740 introduced July 14, 2010)
     
  •  Criteria for assessing civil penalties

  •  Whistleblower protection
     

Download / view the entire Rx-360 summary click here

  Download / view S.3690 click here

  

U.S. H.R. 4678: Foreign Manufacturers Legal Accountability Act of 2010 Minimize

U.S. H.R. 4678: Foreign Manufacturers Legal Accountability Act of 2010

HR4678 was introduced in February 2010 by United States Congressman Sutton and approved by the House Ways and Means Committee in July 2010.  The Energy and Commerce and House Agriculture Committees will now have the opportunity to consider the bill before it goes to the full House.  This is a companion bill to one that was introduced in the U.S. Senate (S. 1606) in August 2009 by Senator Whitehouse.  The purpose of the bill is to require foreign manufacturers, whose products are imported into the US, to identify “registered agents” who have responsibility to serve as the point of contact for communication of legal proceedings and actions.  Section 3(b) of the proposed legislation states that “A foreign manufacturer or producer of a covered product that registers an agent under this section thereby consents to the jurisdiction of the State and Federal courts of the State in which the registered agent is located for the purpose of any judicial proceeding related to such covered product.”  This will facilitate taking legal action against these manufacturers in the United States.  The bill is not specifically focused on products regulated by the FDA but also covers items governed by the Consumer Product Safety Commission, the Environmental Protection Agency and the National Highway Traffic Safety Administration.     

To download / view the U.S. H.R. 4678, click here
 

To download / view the Rx-360 summary, click here

  

Rx-360 Summary of US Legislation of HR 5740 Minimize

Rx-360 Summary of US Legislation of HR 5740 

Introduction: HR 5740 proposes to give the FDA mandatory recall authority for adulterated or misbranded human and animal drugs.  Currently, the FDA does not have this authority and depends on the company to make and execute recall decisions, albeit in communication with the local district FDA office.  This legislation was introduced on July 14, 2010 by Representative Edolphus Towns, Chairman of the House Committee on Oversight and Government Reform.  Chairman Towns mentioned that he would be introducing this legislation during the May 27, 2010 hearing conducted with regard to the several McNeil Consumer Healthcare recalls of their liquid pediatric formulations made in Fort Washington PA. This draft legislation provides for three recall options.

  • The company may initiate recalls as in the past
     
  • FDA may require a recall when “reasonable probability” exists that “…the drug will cause a threat of serious adverse health consequences or death…”
     
  • FDA may issue a recall order when they have “…credible evidence…that a drug…presents an imminent threat of serious adverse health consequences or death…" 

The sections that address non-delegation of these responsibilities are important to note.  In the situation described in the second bullet point, the responsibility may only be delegated to the district director, or their superior, where the drug involved is located.  In the third bullet, these responsibilities may only be performed by the Commissioner of Food and Drugs, the Principal Deputy Commissioner, or the Associate Commissioner for Regulatory Affairs of the FDA.  Thus, it appears that recall decisions made by FDA are not at the discretion of individual ORA inspectors who may uncover evidence that can ultimately lead to a recall.  In both cases where FDA exercises their recall authority, the company has access to appeal the decision within 24 hours of its issuance and petition for review at an informal hearing to be held within 5 days of the appeal. 

It is unclear if the bill will be considered by the full House of Representatives during 2010.  We will continue to track developments and provide additional updates, as warranted.


 To download / view the FDA's report,
 
click here

To download / view the Rx-360 summary, click here

 

  

FDA Transparency Initiative: Minimize

 FDA Transparency Initiative:

 

Last summer, FDA Commissioner Margaret Hamburg launched the Transparency Initiative to promote openness related to FDA activities and decision making.  Activities in support of this initiative are divided into three phases:  FDA Basics,  Public Disclosure and Transparency to the Regulated industry.  This report focuses on the second phase, Public Disclosure.  The draft report, published in May 2010, identifies twenty-one (21) specific draft proposals for public comment.  FDA believes implementation of these proposals will: 

  • Better explain FDA decisions
  • Provide more data to both doctors and patients
  • Clarify enforcement efforts and actions
  • Support innovation of treatments for rare diseases
The areas covered in this report are broad in scope and address many of the ways in which FDA regulates products.  We have focused only on supply chain items in the attached summary.

 

 

To download / view the FDA's report, click here

To download / view the Rx-360 summary, click here
 

 

  

FDA Draft CMC Guidance: Minimize

FDA Draft CMC Guidance:

 

FDA published a draft guidance entitled “Guidance for Industry, CMC Postapproval Manufacturing Changes Reportable in Annual Reports”  on June 24, 2010.  This appears to represent the beginning of FDA efforts to revise 21 CFR 314.70(d) post approval reporting for NDA and ANDA drugs.  The intent of these changes is to minimize the number of post approval manufacturing supplements that FDA receives and reviews. Another guidance, “Changes to an Approved NDA or ANDA” will be revised to be consistent when this guidance is finalized.  The first few pages of the guidance provide background and reiterate that manufacturers need to comply with all applicable regulations as well as the recommendations in ICHQ7.  The second half of the guidance is Appendix A that provides a 3 ½ page list of changes which now may be submitted in an annual report.  The deadline for submission of comments to FDA on the draft guidance is September 23, 2010.

 

 

To download / view the FDA's guidance, click here

To download / view the Rx-360 summary, click here

 

  

UPS Supply Chain Survey: Minimize

UPS Supply Chain Survey:

United Parcel Service (UPS) conducted its third annual survey regarding Supply Chain challenges.  Results indicate that most companies are actively pursuing global expansion.  Country regulations and product security are cited as the most significant challenges to this effort.  Increasing regulation of the supply chain remains at that top of the list for those who make supply chain decisions.  Product security challenges, including counterfeiting and product theft / diversion, are areas of concern.  Managing costs associated with supply chain management remains the top item for the third year.  This cost management is complicated by the implementation of health care reform and the ongoing economic recession. 
 

To download / view survey results, click here


 

  

The U.S. China Economic and Security Review Commission Biopharma Report Minimize

The U.S. China Economic and Security Review Commission contracted with the NSD Bio Group LLC to prepare this report addressing the health and safety aspects of the large number of pharmaceutical and dietary ingredients manufactured and imported from China.  Recent instances of adulterated human medicines and food have highlighted the importance of this link in the pharmaceutical and dietary supply chain.  Over time, China has become the largest supplier of APIs and many dietary supplements such as vitamins.  Although the Chinese regulatory authority, SFDA, has recently improved their infrastructure and requirements, the report notes significant gaps remain before their regulatory oversight process is sufficiently mature, matching that of many western countries.  In addition, the number and variety of such manufacturers in China pose a challenge to FDA oversight.  At the end of the report there are recommendations for FDA to consider that may strengthen their oversight of foreign establishment, especially those in China.

 

To view or download NSD report, click here 

 

To view or download Rx-360 summary of NSD report, click here

 

 

 

  

From Brazil, ANVISA Issues Revised GMPs Minimize

Effective with their publication on April 19, 2010, Brazil revised their pharmaceutical Good Manufacturing Practice requirements.  This replaces the GMPs which had been in place from August 2006.  GMPs for pharmaceutical products from the Mercado Com'un del Sur (MERCOSUL)areas are incorporated into this revision.  MERCOSUL represents a regional trade agreement including the countries of Argentina, Brazil, Paraguay, Uruguay and Venezuela.  Bolivia, Chile, Colombia, Ecuador and Peru currently have associate member status.  

Rx-360 has created a slide deck that addresses only the aspects of the revised GMPs which are relevant for supply chain, and represent additions to existing requirements.

The ANVISA GMP document can be downloaded by clicking here

   

The Rx-360 Summary can be downloaded by clicking here

 

  

US FDA Final Guidance - Standards for Securing the Drug Supply Chain - Standardized Numerical Identification for Prescription Drug Packages Minimize

The amendments to the FD&C Act in 2007 required FDA to take actions to secure the supply chain, including development of a standardized numerical identifier (SNI) which the current guidance addresses.  FDA took many of the industry comments into account, modifying the draft guidance which originally published in January 2009.  The guidance addresses SNIs for package level identification, provides flexibility in the type of data carrier, does not require incorporation of either batch number or expiry and is compatible with the GS1 GTIN and AI-21 standards.  For additional detail please see: 

Click here to read FDA Guidance

 

Click here to read Rx-360 Summary of FDA Guidance

  

Guideline for the Production and Control of Specified Starting Materials Minimize

The World Health Organization (WHO) has published a draft guideline for comment, entitled Guideline for the Production and Control of Specified Starting Materials.


This guidance includes an extensive introduction section which provides both background and context for the information on “specified starting materials”.  WHO defines these materials as any substance which is primarily or mainly used as a starting material for the production of an API, but which itself could be used directly as an API.


If the “specified starting material” is itself an API then it should conform to the existing monograph in a recognized pharmacopeia.  If the API is not supported by a pharmacopeia monograph, then appropriate specifications should be developed and justified by the manufacturer.  


If the material is used in the production of an API then the quality attributes and specifications should be determined by the API manufacturer and the material should be fit for its intended use. 


Viral safety and TSE data should be carefully considered if the starting material is animal derived.


Quality Control for compounds used as specified starting materials should address impurity profiles, isomers, residual solvents and other impurities that may be carried thru to the resulting API.


API manufacturers are encouraged to take a risk based approach in setting specifications for these materials, considering the number and type of unit operations between introduction of the material and production of the resulting API.  For additional detail, please go to the following links:

 

Click here for the WHO Guidance Document  


Click here for the Rx-360 Summary of the WHO Guidance Document

 

  

Rx-360 Summary of US Congressional Hearing - Drug Safety an Update from FDA Minimize

On March 10, 2010 the House of Representatives Committee on Energy and Commerce, Subcommittee on Health held a hearing: "Drug Safety: An Update from FDA".  Joshua Sharfstein, Principal Deputy Commissioner of the FDA, provided an update on the FDA’s current challenges and accomplishments in the area of drug safety.  Dr. Sharfstein addressed FDA’s activities with respect to the 2007 FDAAA which provided additional legal authority and resources to FDA.  He also addressed the challenges presented by a global supply chain within the pharmaceutical industry. 

For additional information, click here.

  

European Union's Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use Minimize

Rx-360 has prepared summaries of proposed revisions to the European Union's Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use (Chapter 1 - Quality Management System and Chapter 2 - Personnel).

 

     To view or download Chapter 1 click here
     To view or download Rx-360 Summary of Chapter 1
click here

     To view or download Chapter 2 click here
     To view or download Rx-360 Summary of Chapter 2
click here

  

EC Directive 2001/83/EC to Prevent Falsified Medicines Updated Minimize

The EC is modifying their Directive 2001/83/EC to prevent the introduction of falsified medicines into the legal supply chain for medicinal products.  Several draft revisions have been produced with the most recent revision dated April 13, 2010.  Ensuring an accurate definition of what constitutes a “falsified medicinal product” has been a concern particularly from WHO and developing countries’ generic companies who may trans-ship product thru the European Union.   This definition must adequately protect intellectual property but not interfere with legitimate trade of pharmaceutical products.  We will continue to update RX-360 members as additional revisions are published.    

The EC Directive can be downloaded by clicking here

The Rx-360 Summary can be downloaded by clicking here

 

  

 

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