Monday, September 22, 2014
2014 Summaries Minimize
Report Number

Description Date
495
Read the Rx-360 Summary of the FDA UDI Final Rule

26-Aug-14
493
PIC/S Committee has adopted a Guide on Good Distribution Practice

21-Aug-14
484


The Active Pharmaceutical Ingredient Committee (APIC) Published a draft “How to do” document on GDP

 

09-Jul-14
483
EMA has published a qualified person’s declaration concerning GMP compliance of the active substance manufacture

08-Jul-14
481
Webinar and Rx-360 Summary of Guidance on Drug Supply Chain Security Act Implementation: Identification of Suspect Product and Notification

25-Jun-14
478
WHO Technical Documents for Storage and Transportation of Temperature Sensitive Products
 
13-Jun-14
 473
Listen to a Complimentary Rx-360 Webinar on Upstream Supply Chain Security

23-May-14
 469
Read the Rx-360 Summary of US FDA Guidance for Industry: ANDAs: Stability Testing of Drug Substances and Products and FDA Questions and Answers

19-May-14
 456
Read the Rx-360 Summary of the EC Revised GMPs Chapter 6, Quality
 
 
10-Apr-14 
455
Read the Rx-360 Summary of the EU GDP Questions and Answers 

10-Apr-14
455
Read the Rx-360 Summary of the FDA's Guidance on Allowable Fill Volume Excesses in Vials

25-Mar-14
454
Read the Rx-360 Summary of the GAO Drug Shortage Report
 
12-Mar-14
453
Read the Rx-360 Summary of the First Annual Report on Drug Shortages

12-Mar-14
452
Read the Rx-360 Summary of the First FDA Annual Report on the Inspection of Registered Establishments

06-Mar-14
451
Read the Rx-360 Summary of the First Annual Report on Drug Shortages
 
26-Feb-14
450
Draft EU GMP Annex 15 for Qualification

24-Feb-14
446
EU Q&A on Importation of APIs

04-Feb-14
443
Read the Free Rx-360 Summary of the 2013 UPS Supply Chain Survey

13-Jan-14

 

  

FDA Proposed Rule to Remove the General Safety Test requirements for Biological Products Minimize
 

FDA Proposed Rule to Remove the General Safety Test requirements for Biological Products.  FDA is proposing to remove the requirement for General Safety Testing required in 21CFR 610.11, 610.11a and 680.3(b).  FDA is proposing to remove these requirements because they are duplicative of requirements in BLAs for influenza virus, allergenic extracts and other biological products and don’t provide any additional protection of public health.  Even though the general safety tests are proposed to be removed from the above parts of 21CFR, the firms must still comply with testing as described in their approved BLAs.  Manufacturers may submit a supplement to their BLA to remove or modify this test requirement.  Decisions will be made on a case-by-case basis.

To read or download FR Notice,  click here

 

 

  

FDA Guidance for Industry, Unique Device Identification System Minimize

 

FDA Guidance for Industry, Unique Device Identification System



CBER and CDRH published Guidance for Industry, Unique Device Identification System:  Small Entity Compliance Guide on August 13, 2014. The guidance provides information on the implementation of the Unique Device Identification (UDI) system, including guidance for small entities as required by the Small Business Regulatory Enforcement Fairness Act of 1996.  In addition to information regarding implementation of the UDI requirements, the guidance provides:

  • Several definitions including relevant information in footnotes (page 6 – 10)
  • A table of exceptions and alternative to the UDI requirement (page 18-19)
  • A table listing the sections of 21CFR that were modified, and a description of the modifications made as a result of the UDI final rule (page 22)A table listing specific dates of compliance for the requirements of the UDI rule (page 23)

 

CBER and CDRH also publishedUnique Device Identifier System: Frequently Asked Questions, Vol. 1on August 20, 2014.  It includes answers to thirty-one (31) questions organized according to the key provisions of the rule.  Identifying this document as Vol. 1 suggests that additional Q&As will be published in the future.

 

To view or download the FDA Unique Device Identification
System Final Rule,
click here 

To view or download the FDA's FAQs, click here

To view or download the FDA Small Business Guide, click here

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




 

  

FDA Guidance for Industry: Design Considerations for Devices Intended for Home Use Minimize

FDA Guidance for Industry:  Design Considerations for Devices
Intended for Home Use

 

Guidance for Industry:  Design Considerations for Devices Intended for Home Use published in the Federal Register on August 5, 2014.  This guidance finalizes the draft that was published for comment in December, 2012.  The scope section does not specifically reference combination products.  However, it is logical to assume that the general concepts and considerations should be applicable to combination products that are intended for use outside of a formal healthcare setting.  

The guidance includes an extensive list of references (pages 19-24) that includes standards mentioned in the guidance that are published by standards setting organization including ANSI, AAMI, ASTM and IEC. The guidance includes sections on:

  • Environmental Considerations 
  • User Conditions 
  • Design Consideration with a Large Section Focused on Electrical Issues
  • Human Factors, Labeling and Post Market Considerations


To view or download the FDA Guidance, click here

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

 

 

  

PIC/S GDP Guidance Minimize
PIC/S Committee has adopted a Guide on Good Distribution Practice 
 
  The PIC/S Committee has adopted a Guide on Good Distribution Practice (GDP), which will enter into force on 1st June 2014. The PIC/S GDP Guide is based on the EU GDP Guide.

The PIC/S GDP Guide is a non-binding guidance document because PIC/S is not a regulatory authority in the sense of the competent authorities in the EU and the regulatory authorities in the US, Canada, Australia and Japan. 

Each of the competent authority PIC/S members will make the decision regarding whether the guideline is to be implemented and enforced.  Several regulatory authorities outside of the EU are members of PIC/S including the US, Canada, Japan and Australia.  How this will be applied by those authorities is unknown at this time.
 
While the PIC/S guideline is based upon the EU GDP Guide and Chapters 1 through 9 have the same structure as the EU guideline, the following differences are noted with regard to the PIC/S GDP Guideline:
  • EU specific references have been removed
  • Import activities are included
  • “Responsible Person” is replaced by designated responsible person(s)
  • Contains more references to risk management throughout
  • Additional reference are made to record(s)/procedure(s)s that should be maintained
  • Batch/expiry guidance is based upon national legislation
  • Contains more general requirements for import/export (not EU specific)
  • Includes more detail on actions taken upon identification of falsified medicines, including recall guidelines
  • Does not contain a chapter on Brokers as in the EU Guide
  • Lists additional glossary terms; including temperature, with defined ranges

To view or download the PIC/S GDP Guidance, click here

  

  

How To GDPs Minimize
  The Active Pharmaceutical Ingredient Committee (APIC) of the European Chemical Industry Council (CEFIC), the trade association representing European chemical manufacturers, recently issued a draft “How to do” document to provide guidance on good distribution practices (GDPs) for active pharmaceutical ingredients (APIs).  


The document is available here: 

http://apic.cefic.org/pub/GDPHowtoDo_201405.pdf

and it interprets the WHO Guideline: “Good Trade and Distribution Practices for Pharmaceutical Starting Materials” and the Guidelines on the Principles of Good Distribution Practices for Active Substances for Medicinal Products for Human Use issued by the European Commission (DG Sanco).  The document was prepared by industry experts from APIC/CEFIC and intends to “provide examples of commonly applied solutions and practical assistance on how requirements and recommendations can be met and/or interpreted.”

  

QP Declaration Minimize
  The European Medicines Agency issued on 21 May 2014 “The QP Declaration Template” and guidance for the template for the qualified person’s declaration concerning GMP compliance of active substance manufacture.  Marketing authorizations require a Qualified Person (QP) declaration to confirm that an active substance has been manufactured in accordance with Good Manufacturing Practice (GMP) for medicinal products for human and veterinary use.  

The declaration should be based upon an on-site audit of the active substance manufacturer and is required to be submitted with all applications for new marketing authorizations, renewals, and submissions of relevant quality variations.
 
The template provides a suitable means for documenting confirmation that the active substance manufacture complies with the GMP requirements and is intended to harmonize the format for the declaration, to preclude questions during assessment, and to enhance the efficiency of the regulatory process.

 

 
  

Rx-360 Summary of Guidance on Drug Supply Chain Security Act Implementation: Identification of Suspect Product and Notification Minimize
 

FDA published a draft guidance, Guidance for Industry, Drug Supply Chain Security Act Implementation:  Identification of Suspect Product and Notification.   This guidance is published to support implementation of requirements in the November 2013 Drug Supply Chain Security Act (DSCSA) amendments to the FD&C Act.  The purpose of the guidance is to assist manufacturers, re-packagers, wholesale distributors and dispensers in the identification of suspect product, notification of both trading partners and FDA and terminating of the same notifications.  Beginning January 1, 2015, “…trading partners, upon determining that a product in their possession or control is illegitimate, to notify FDA and all immediate trading partners…not later than 24 hours after making the determination.”  


Download or View the Rx-360 Summary of the Draft Guidance, click here

 

CDER SBIA Webinar on
“An Overview of FDA’s Draft Guidance - Drug Supply Chain Security Act Implementation:
Identification of Suspect Product and Notification.” - July 1, 2014

On Tuesday July 1, 2014, at 1PM (EDT), CDER SBIA will host a webinar entitled “An Overview of FDA’s Draft Guidance - Drug Supply Chain Security Act Implementation: Identification of Suspect Product and Notification.” 

FDA published a notice in the Federal Register announcing the availability of the draft Guidance for Industry - Drug Supply Chain Security Act Implementation: Identification of Suspect Product and Notification. The Drug Supply Chain Security Act of 2013 requires FDA to issue draft guidance to help certain trading partners (manufacturers, repackagers, wholesale distributors, and dispensers) identify suspect products,  and must begin notifying FDA if it suspects it has illegitimate product in its possession on January 15, 2015. This guidance also provides information for supply chain stakeholders about how to notify FDA when they determine that they have an illegitimate product, and how to terminate that notification, consulting with FDA, should it no longer be necessary.

The purpose of this webinar is to provide an introduction and overview of FDA’s recently issued draft guidance, “Drug Supply Chain Security Act Implementation: Identification of Suspect Product and Notification.”  This is the first guidance issued under the Drug Supply Chain Security Act.

Additional information is located at:http://www.fda.gov/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/ucm402366.htm 

 

To register for this Event, please go the following link:https://collaboration.fda.gov/sbia0701/event/registration.html

(Registration password needs to be 8 characters and alphanumeric)

 

Note: Your registration acknowledgement will include the webinar access link. 

Audio will broadcast from your computer speakers.

Closed captioning will be provided.

Please note: There is a user capacity limit for this webinar. For those who cannot enter the webinar, please know that it will be recorded and a link will be posted to this page.

 

Questions/Comments can be submitted live via a Q/A chat window.

- Webinar access link: https://collaboration.fda.gov/sbia0701/event/registration.html

FR Document: 2014-13544

Docket ID: FDA-2014-D-0609

Draft Guidance: Drug Supply Chain Security Act Implementation: Identification of Suspect Product and Notification

  

For questions concerning the webinar, please contact CDER SBIA at:  

(866) 405-5367 | (301) 796-6707

  

CDER SBIA webinar series:http://www.fda.gov/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/ucm070334.htm

Adobe, the Adobe logo, Acrobat and Acrobat Connect are either registered trademarks or trademarks of Adobe Systems Incorporated in the United States and/or other countries.

  

Brookings Meeting Proceedings on Quality Metrics Minimize


The Engelberg Center for Health Care Reform at Brookings hosted a meeting to discuss Quality Metrics in May.

Meeting Summary: Quality assurance and control play an essential role in the pharmaceutical manufacturing process, by ensuring that patients are provided with medications that are safe, effective, and produced at a high level of quality. Despite recent advances in the manufacturing sector, quality issues remain a frequent occurrence, and can result in recalls, withdrawals, or harm to patients. Quality issues have also been linked to the rise in critical drug shortages. 


However, recent legislative actions and regulatory reforms have provided additional tools for regulators and manufacturers to confront these issues. Included among these tools is a program aimed at developing and implementing a set of standardized manufacturing quality metrics for use by the U.S. Food and Drug Administration (FDA). The establishment and collection of these metrics could provide various stakeholders – from industry to regulators – with greater insight into the state of quality at a given manufacturing facility, and allow stakeholders to better anticipate and address quality issues while simultaneously reducing unnecessary regulatory burden.

To read the entire proceedings, click here.

 

  

QP Declaration Template Minimize
 

The European Medicines Agency issued on 21 May 2014 “The QP Declaration Template” and guidance for the template for the qualified person’s declaration concerning GMP compliance of active substance manufacture.  

Marketing authorizations require a Qualified Person (QP) declaration to confirm that an active substance has been manufactured in accordance with Good Manufacturing Practice (GMP) for medicinal products for human and veterinary use.  The declaration should be based upon an on-site audit of the active substance manufacturer and is required to be submitted with all applications for new marketing authorizations, renewals, and submissions of relevant quality variations.

The template provides a suitable means for documenting confirmation that the active substance manufacture complies with the GMP requirements and is intended to harmonize the format for the declaration, to preclude questions during assessment, and to enhance the efficiency of the regulatory process.

 

  

WHO Guidance on Shipping Temperature Sensitive Materials Minimize
  The WHO has released for review a set of technical supplements to the WHO Technical Report Series, No. 961, 2011 Annex 9: Model guidance for the storage and transport of time and temperature–sensitive pharmaceutical products. These supplements have been written to amplify the recommendations given in the specific Sections of the Technical Report Series.  Comments are invited on the attached supplements and due by 30 June 2014.


To view or download the WHO Documents, click on the file name below:

 

1. Temperature and Humidity Monitoring Systems for Transport Operations

2. Temperature and Humidity Monitoring Systems for Fixed Storage Areas

3. Designed and Procurment of Storage Facilities

4. Maintenance of Storage Facilities

5. Selecting Sites for Storage Facilities

6. Estimating the Capacity of Storage Facilities

 

 

 

  

EMA Draft Validation Guidance Minimize

EMA Guideline on Process Validation for the Manufacture of Biotechnology-derived Active Substances and Data to be Provided in the Regulatory Submission 

The European Medicines Agency (Committee for Medicinal Products for Human Use published Guideline on Process Validation for the Manufacture of Biotechnology-derived Active Substances and Data to be Provided in the Regulatory Submission for consultation on April 25, 2014.  Comments are due by October 31, 2014.  

This new draft guidance addresses the data requirements for validation of biotechnology drug substances and advises where that data is to be included, within the regulatory filings. 
The scope of the guideline includes “…recombinant proteins and polypeptides, their derivatives, and products of which they are components (e.g. conjugates)”. It may also apply to other biologic products such as vaccines and blood products.  The EMA guidance is clear that a company can use either a traditional approach or an enhanced approach, or some combination of the two to achieve process validation and establish a state of process control.
 
The guidance addresses the role of process development data leading up to process validation and ongoing verification.  It also addresses process validation including process evaluation, process verification and ongoing verification. Process evaluation addresses the evaluation of selected steps, where appropriate, operating at worst case or abnormal conditions to demonstrate robustness of the process to produce product of the intended quality.
 
Points to consider in process validation, section 6, addresses upstream and downstream processes, multi-facility production, single use equipment, multiple harvest processes, reprocessing and storage/transportation of intermediates and active substances. For single use equipment, consideration should include the impact of leachables and extractables.  When market demand requires multifacility production, “the adapted process should be able to produce comparable outputs within the same imput range.”  One must also be able to demonstrate the equivalence of product from differing sites.  In line with the recent focus on the GDP guideline on transport of cold chain product, this guidance states that transportation of both intermediates and drug substance should be validated and should demonstrate “…that the quality of the intermediate or active substance will not be altered if transported according to the defined conditions.” 
 
The Guidance also includes a Glossary and list of References which includes, ICHQ5A(R1), Q6B, Q7, Q10 and Q11

To view of download the guidance, click here
  

ANDAs: Stability Testing of Drug Substances and Products Questions and Answers Minimize

US FDA Guidance for Industry: ANDAs: Stability Testing of Drug Substances and Products and FDA Questions and Answers

 

The USFDA has published “Guidance for Industry, ANDAs: Stability Testing of Drug Substances and Products, Questions and Answers” in May 2014.  This guidance contains questions and answers from public comments generated during the drafting of “Guidance for Industry, ANDAs: Stability Testing of Drug Substances and Products” the final document being published in June 2013 for generics. The guideline recommends that ANDAs, and DMFs (Drug Master Files) which support ANDAs, follow ICH stability guidelines Q1A(R2), Q1B, Q1C, Q1D, Q1E. The implementation date of the Q&A is June 20, 2014.


The Q&A covers 5 topic areas and is intended to clarify stability testing data recommendations for abbreviated new drug applications (ANDAs) found in the short guideline.

  • The General section mainly addressing timing, amount of data, and number of lots to use for stability studies
  • The Drug Master File  section covers the impact of guideline to DMFs
  • The Drug Product Manufacturing and Packaging section takes up most of the Q&A and touches on inclusion of secondary packaging in stability studies, batch size and batch definitions, definition of small scale for various dosage forms as well as “small scale” development guidance.
  • The section on Amendments to Pending ANDA Application states amendments will be held to the standards in place of original submission.
  • The Stability Studies section includes guidance on the technical aspects of stability studies such as time points, storage, containers and testing.

To view the Guideline Q&A, click here

To view the original Guidance, click here

 

 

  

European Commission (EC) published the revised Chapter 6: “Quality Control” of the Volume 4 Minimize
 

European Commission (EC) published the revised Chapter 6: “Quality Control” of the Volume 4

Rx-360 Issued: 11-April-2014

On the 28th March 2014, the European Commission (EC) published the revised Chapter 6: “Quality Control” of the Volume 4 of the guidelines for Good Manufacturing Practices (GMP) for Medicinal Products for Human and Veterinary Use. The document will be effective on the 1st October 2014.

The revised Chapter 6 on quality control contains a new section on analytical method transfer (section 6.37: “Technical transfer of testing methods”) that points to the need for verifying that the test method(s) comply with those as described in the Marketing Authorisation (MA), establishing a method transfer protocol and provide recommendations on what the protocol should contain.

Also added is an emphasis on the importance of investigating out of specification (OOS) trends in laboratory data. The final document notes that a procedure for the investigation of OOS, out of trend (OOT) results and “anomalous results” should be in place and that the results should be addressed and recorded in a manner that permits trend evaluation.

The revision introduces the notion of a risk based approach regarding the sampling plans.

In section 6.23 and 6.24, the revised Chapter 6 set forth requirements for culture media and strains management.

Moreover, the document highlights that the samples should be managed in order to minimize risk of mix-up and to protect from adverse storage conditions.

Finally, Chapter 6 states that documentation retention should be performed according to Chapter 4 “Documentation” of the Volume 4.

 

To view or download the EC Revised Chapter 6, click here

 

  

EU – Good Distribution Practice for Medicinal Products for Human Use – Questions and Answers Minimize
 

EU – Good Distribution Practice for Medicinal Products for Human Use – Questions and Answers

Rx-360 Issued: 10-April-2-14

On 28 March 2014 the European Commission published a question and answers document related to the new guideline on Good Distribution Practice of medicinal products for human use applicable as of November 2013.

The Q&A document contains 25 questions and answers. The questions focused mainly around:

  • Competence and training of personnel (chapter 2)
  • Segregation of products, temperature and environmental control, alarms and deviations (chapter 3)
  • Qualification of customer, verification of authorization for sale (chapter 5)
  • Control of returned products and recall procedure (chapter 6)
  • Transport requirements (temperature, safety) (chapter 9)

Some of the questions are simply for clarification and confirmation. Other questions may have become the basis for some discussion:

  • Question 5 (chapter 3.2(3)): It was confirmed that falsified, expired, recalled and rejected products need a physical segregation in any case. A validated computerized system (electronic segregation) cannot substitute in these cases.
  • Questions 7 & 8 refer to chapter 3.2.1. about temperature and environment control. The EU commission highlights the importance of risk assessments as basis for the design of temperature mapping studies and the positioning of monitoring sensors. Further clarification on the design of mapping studies was given (e.g. studies to be performed in different seasons).
  • Questions 13 & 14 are related to product authorization for sale (chapter 5.4.(3)). Different requirements are applicable dependent on the origin of the product (EU member state or not). But in any case the wholesalers need to verify that a batch of medicinal products is authorized for sale in the target state (provision applicable today independent of potential future implementation of safety features allowing traceability through a database).

Question 22 (chapter 9.2.(1)): Some stakeholders proposed to allow transport conditions which may deviate from the standard storage conditions, e.g. greater temperature range for a limited time frame. The EU Commission clearly states that this procedure would not be acceptable.

To view or download the EU GDP Document, click here

 

  

Guidance for Industry, Allowable Excess Volume and Labeled Vial Fill Size in Injectable Drug and Biological Products Minimize
 

Rx-360 Issued: 25-March-2014

FDA recently published a draft Guidance for Industry, Allowable Excess Volume and Labeled Vial Fill Size in Injectable Drug and Biological Products.  Comments are due to FDA by June 12, 2014.  This guidance applies to parenteral drug product provided in vials and is not applicable to drug product provided in pre-filled syringes and intravenous infusion bags.  Both original NDAs, BLAs, ANDAs and their supplements are included within the scope of this draft guidance.  FDA is concerned about “inappropriate excess volume and labeled vial fill sizes” may contribute to microbial contamination of drug product and possible medication errors.   

In this guidance, FDA notes that existing regulations require that sponsors/applicants comply with the “excess volume” recommendations in the USP <1151> for drugs in ampules and vials, intended for injection.  If the applicant chooses to deviate from the USP requirements, they must provide justification.

To view or download the FDA Guidance, click here

To view or download the Rx-360 Summary of 
the FDA Guidance
click here

 

  

DRUG SHORTAGES, Public Health Threat Continues, Despite Efforts to Help Ensure Product Availability Minimize
 

DRUG SHORTAGES, Public Health Threat Continues, Despite Efforts to Help Ensure Product Availability

Rx-360 Issued: 12-March-2104

In 2012, FDASIA provided FDA with additional authority to address drugs shortage and also required GAO to study the drug shortage situation.  The GAO recently published a report: DRUG SHORTAGES, Public Health Threat Continues, Despite Efforts to Help Ensure Product Availability.  In this report GAO evaluates the high level causes of drug shortages and their impact on public health, evaluates the effectiveness of actions that FDA has taken to prevent and mitigate the impact of drug shortages, and makes recommendations for FDA to enhance its oversight of drug shortages.  

The GAO report also reviews economic causes of drug shortages, particularly for generic sterile parenteral products.  GAO acknowledges the progress that FDA has made in preventing shortages and mitigating their impact and suggests that FDA use their data to “…proactively identify drug shortage risk factors.”

 To view or download the GAO Report, click here

To view or download the Rx-360 Summary of
the GAO Report
click here

  

FDA Annual Report on the Inspection of Registered Establishments Minimize
 

FDA Annual Report on the Inspection of Registered Establishments

Rx-360 Issued: 06-March-2014

Section 705 of FDASIA, passed in July 2012, requires that FDA report annually on the inspection of registered establishments and post the information on their web site.  The reports are due no later than February 1 for the prior fiscal year.  This is the first of the reports and addresses the inspection activities of CDER, CBER, CVM and CDRH registered establishments in FY 2013.  The report does not cover establishments that manufacture only excipients because FDA databases do not current include these data.  Data in the report include:

  • Number of registered establishments
  • Number of foreign and domestic establishment inspections and
  • Percentage of the budget used to fund these inspections

To view or download the FDA Report, click here

To view or download the Rx-360 Summary of the FDA Reportclick here

 

  

First Annual Report on Drug Shortages Minimize
 

First Annual Report on Drug Shortages

Rx-360 Issued: 26-February-2014

On February 5, 2014, the FDA provided their First Annual Report on Drug Shortages to Congress as required by Section 1002 of FDASIA.  FDA believes that the increased notifications resulting from action by the Administration, Congress and FDA has allowed them to respond more effectively to shortages and potential shortages.  Pages 1-5 summarize the legal authority in this area and the guidances and actions FDA has taken so far to prevent and mitigate drug shortages.  

  FDA provides data on actions in this area, including but not limited to:
  • 39 different manufacturers notified FDA of 202 potential drug shortages.
  • The Office of Generic Drugs (OGD) expedited review of 118 applications including 62 ANDAs and 56 supplements; the office of biological products expedited review of 7 supplements; in total CDER expedited review of 177 applications that includes ANDAs/NDAs and supplements in the first three quarters of calendar year 2013.
  • 56 inspections were prioritized based on the applications / supplements that were granted expedited review.
  • Figure 1 shows the number of new drug shortages annually between 2005 and Q1-3 of 2013.  These increased to a high of 251 in 2011, decreased to 117 in 2012 and 38 for the first three quarters of 2013.  They conclude that “…in the first three quarters of 2013, we have prevented 140 shortages.”

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

To view or download the FDA report, click here

 

 

  

Draft EU GMP Annex 15 for Qualification and Validation Minimize

Draft EU GMP Annex 15 for Qualification and Validation

Rx-360 Issued: February 24, 2014

The EU has published for consultation Annex 15: Qualification and Validation (Volume 4 of Guidelines for GMP for Medicinal Products for Human and Veterinary Use). The draft comment period ends end of May 2014.  The revision takes into account changes to Part 1 of the EU GMP Guide, Annex 11, ICH documents Q8-11, the EMA Process Validation draft guidance, and changes in manufacturing technologies.  

The draft now includes principles drawn from ICH Q8, Q9, Q10 and Q11, including knowledge management (ICH Q8 & Q10), science and risk-based approaches (ICH Q9) to support lifecycle validation & qualification activities, and the use of a design space (ICH Q8) for Process Validation.

Other key points are:

  • Retrospective validation and the notion of revalidation are gone completely
  • User Requirement Specifications (URS) have been added to the section on Qualification for Facilities and Equipment, along with Factory Acceptance Testing (FAT) and Site Acceptance Testing (SAT)
  • Process Validation is divided into ‘Traditional’ and ‘Continuous Process Verification’ with a hybrid of the two allowed, as per the 2012 draft CHMP NfG on Process Validation
  • For the traditional validation approach, the number of batches manufactured and the number of samples taken should be based on quality risk management principles. This indicates a move away from the previous rule which required three validation batches
  • The term “ongoing process verification” is equated to “continued process verification”
  • "Bracketing" approaches for Process Validation can be used if justified
  • There is a new section on Verification of Transportation. Since validation of transport may be challenging due to the variable factors involved, continuous monitoring of critical environmental conditions should be performed. A risk assessment should be performed which also considers the impact of conditions other than temperature (e.g. humidity, vibration, handling)
  • A “visual check for cleanliness” may no longer be the only criterion for a cleaning validation
  • Cleaning validation is required to be based on a toxicological evaluation to determine the product specific permitted daily exposure (PDE) value, as per the drafts of Chapters 3 & 5 and the CHMP Guideline on setting health based exposure limits
  • The Annex no longer looks for three consecutive batches to demonstrate that the cleaning process is validated. It now states that cleaning process be carried out an “appropriate number of times based on a risk assessment”
  • New concept of cleaning verification for infrequently manufactured or for investigational products 
  • New sections added on:
    1. Ongoing Process Verification during Lifecycle
    2. Verification of Transportation
    3. Validation of Packaging
    4. Qualification of Utilities
    5. Validation of Test Methods

 

To View or Download the Draft of Annex 15, Click Here

 

  

Assessing the Risks of Counterfeiting and Illicit Diversion for Health Care Products Minimize

Rx-360 Summary of Michigan State University Center for Anti-Counterfeiting and Product Protection Risk of Counterfeiting Report



Rx-360 Issued: 09-February-2103

Michigan State University Center for Anti-Counterfeiting and Product Protection published a report titled “Assessing the Risks of Counterfeiting and Illicit Diversion for Health Care Products” in November 2013.  This report addresses the multiple risks of counterfeit and diverted health care products including adulteration with dangerous chemicals, and diluted / sub-potent APIs and dosage form.  The adulterations can happen either through inadvertent GMP failures or through intentional economic motivated adulteration.  Further complicating this issue is the fact that legitimate product that is not maintained under appropriate environmental conditions or handled incorrectly, as may happen with diverted health care products, may lose potency and become ineffective or even harmful.  

The paper identifies potential questions that should be considered in determining the potential risk to patients from a counterfeit or diversion incident (see pages 3-8).  Answers to these questions identify areas of concern that should be considered to mitigate the identified risks.  Such activities are meant to be ongoing and reviewed frequently as the landscape for these type of illegal activities changes rapidly.

To view or download the summary, click here

To view or download the report, click here

 

  

Flash Report re EU Q&A on Importation of APIs Minimize

EU Q&A on Importation of APIs

 

The Falsified Medicines Directive came into force in Europe in January 2013. Among the Directive’s requirements is the stipulation that APIs imported into the European Union meet equivalent GMPs to those applied in the EU.  To implement this requirement, manufacturers must obtain certification from the competent authority in the country where the API is manufactured that they were made in compliance with GMPs equivalent to those of the EU.  Alternatively, countries of origin may apply for exemption from this rule for APIs manufactured within their borders.  

 

To assist manufacturers, the European Commission published version 5.0 Questions and Answers regarding Importation of Active Substances for Medicinal Products for Human Use on November 13, 2013 which adds two new questions and answers - 33 and 34: 

33. QUESTION:WHAT HAPPENS WHEN AN ACTIVE SUBSTANCE MANUFACTURING SITE COVERED BY A WRITTEN CONFIRMATION IS FOUND GMP NON-COMPLIANT FOLLOWING AN INSPECTION BY A EU MEMBER STATE?

Answer: A statement of GMP non-compliance issued by a EU Member State for a specific site and API supersedes the corresponding written confirmation until the noncompliance is resolved.

34. QUESTION: WHERE CAN I FIND A LIST OF ACTIVE SUBSTANCE MANUFACTURING SITES THAT RECEIVED STATEMENTS OF GMP NON-COMPLIANCE?

Answer: Statements of GMP non-compliance are stored in the EudraGMDP database (http://eudragmdp.eudra.org/inspections/displayWelcome.do). They are currently accessible only by EU national competent authorities, but are expected to become publicly available by end of 2013.  Until then, a list of active manufacturing sites that received a statement of GMP noncompliance can be found here: http://ec.europa.eu/health/humanuse/quality/index_en.htm#ias

The EudraGMDP database referenced above now includes summary reports and reasons for non-compliance status identified during inspections.  It may be found at:

http://eudragmdp.ema.europa.eu/inspections/gmpc/searchGMPNonCompliance.do.

 

  

UPS Supply Chain Survey Minimize

Rx-360 Summary of UPS Supply Chain Survey

UPS has issued its sixth annual “Pain in The (Supply) Chain Survey.”  The survey results report that a majority of North America logistic executives view increasing regulations (54%) and changes in healthcare legislation (53%) as the top pain points for them.  These were also leading pain points in Western Europe.  In Asia, increased regulations and increasing competition were identified by over 50% of the survey responders.  Globally, half of the responders indicated they are still feeling the impact of the economic downturn.  Common themes in the survey include:

  • Logistics professional around the world identified accumulating supply chain and regulatory expertise as a best practice to address supply chain concerns. 
  • Utilizing new technology is also a common theme.  This includes order management, web ordering systems and temperature sensitive technologies. 
  • Companies are expecting to significantly increase investment in web ordering systems, e-pedigree and serialization technologies and security specific technologies over the next 5 years.

Click here to view of the UPS survey results

Click here to view the Rx-360 Summary

 

  

 

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