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Tuesday, October 8, 2013
21 CFR 11: Complete Guide to International Computer Validation Compliance for the Pharmaceutical Industry
http://bookos.org/dl/560842/d4d4d5
Validating Corporate Computer Systems: Good IT Practice for Pharmaceutical Manufacturers
http://bookos.org/dl/568488/6b98fa
Good Design Practices for GMP Pharmaceutical Facilities
http://bookos.org/dl/563697/97e4a8
Wednesday, August 28, 2013
21 CFR Part 11
New EU GMP Guide Annex 11 "Computerised Systems" & Chapter 4 "Documentation"
NEW: Annex 2: Validation of Databases (DB), Laboratory Information Management Systems (LIMS) and Electronic Laboratory Notebooks (ELN)
NEW: Annex 3: Validation of computers as part of test equipment
GAMP 4 to GAMP 5 -Summary
Sunday, June 12, 2011
Guidance from different agencies(Source:(cGALP))
Guidance document on part 11-Electronic signature & Electronic record & Computer System Validation(CSV)
FDA guidance - General principles of software validation
Computer System Validation(CSV)
21 CFR Part 11 -FDA
NEW: Validation of Computerised Systems - Core Document
NEW: Annex 1: Validation of computerised calculation systems: example of validation of in-house software - Spread sheet/Microsoft Excel
NEW: Annex 3: Validation of computers as part of test equipment
Stability study
The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light, and to establish a re-test period for the drug substance or a shelf life for the drug product and recommended storage conditions. Stability testing is a routine procedure performed on drug substances and products. It is involved at various stages of product development.
In early stages, accelerated stability testing (at relatively high temperatures and/or humidities) can be used as a “worst case” evaluation to determine what types of degradation products may be found after long-term storage.
Testing under more gentle conditions (those recommended for long-term shelf storage), and slightly elevated temperatures, can be used to determine a product’s shelf life and expiration dates.
In these types of studies, the product is analyzed at regular intervals for various parameters, which may include assay of the active ingredient, measurement of known degradation products, dissolution time, appearance, etc.
Stability Guidelines
ICH
Quality Guidelines : (Stability)
Q1A(R2): Stability Testing of New Drug Substances and Products
Q1B: Photostability Testing of New Drug Substances and Products
Q1C: Stability Testing for New Dosage Forms
Q1D: Bracketing & Matrixing Designs for Stability Testing of Drug Substances & Drug Products
Q1E: Evaluation of Stability Data
Q1F: Stability Data Package for Registration Applications in Climatic Zones III and IV - This Guideline withdrawn on June 8, 2006
Guidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms Annex 5, WHO Technical Report Series 863, 1996
MORE
Item 10.1 TRS 937:
Item 10.1, WHO Technical Report Series 937, 2006
MORE
Update, Item 11.1 TRS 908
Item 11.1, WHO Technical Report Series 908, 2003
MORE
Stability testing of active pharmaceuticals ingredients and finished pharmaceuticals products - Annex 2
WHO Technical Report Series 953, 2009
Consultation of Stability studies in a global environment
MORE
USFDA
EMEA
Stability testing of new drug substances and products
TGA
Australian Regulatory Guidelines for Complementary Medicines(ARGCM)
TGA : Questions & answers on the stability testing of Listed complementary medicines
ASEAN
Stability study of drug product
GCC
Stability testing of drug substances and pharmaceutical products
Decision Tree for Data Evaluation for Retest Period or Shelf Life Estimation for Drug Substances or Products (excluding Frozen Products)
Case 1 : No significant change in accelerated
a) No or little change in long term and accelerated
Extrapolation (Y) = up to 2X, but not exceeding X + 12 months;
or if refrigerated, Y = up to 1.5X, but not exceeding X + 6 months
b) Change in in long term & acclerated
i)If backed by statistical analysis and relevant supporting data;
Extrapolation (Y) = up to 2X, but not exceeding X + 12 months;
or if refrigerated, Y = up to 1.5X, but not exceeding X + 6 months
ii)If backed by relevant supporting data;
Extrapolation (Y) = up to 1.5X, but not exceeding X + 6 months;
or if refrigerated, Y = up to X + 3 months
Case 2 : Significant change within 6 month accelerated
a) if refrigerated, and significant change within 3 months - No extrapolation
b) if refrigerated, and no significant change within 3 months- No extrapolation
c) if not refrigerated and significant change at intermediate - No extrapolation
d) if not refrigerated and no significant change at intermediate condition
i) If backed by relevant supporting data:Y = up to X + 3 months
ii) If backed by statistical analysis and relevant supporting data
Y = up to 1.5X, but not exceeding X + 6 months
Note:
"Significant change" for a drug substance is defined as failure to meet its specification
In general, "significant change" for a drug product is defined as:
1. A 5% change in assay from its initial value; or failure to meet the acceptance criteria for potency when using biological or immunological procedures;
2. Any degradation product’s exceeding its acceptance criterion;
3. Failure to meet the acceptance criteria for appearance, physical attributes, and functionality test (e.g., color, phase separation, resuspendibility, caking, hardness, dose delivery per actuation); however, some changes in physical attributes (e.g., softening of suppositories, melting of creams) may be expected under accelerated conditions; and, as appropriate for the dosage form:
4. Failure to meet the acceptance criterion for pH; or
5. Failure to meet the acceptance criteria for dissolution for 12 dosage units.
FIP Position Paper on Qualification of Paddle and Basket Dissolution Apparatus -To read click the link FIP Position paper dissolution
FDA publishes guidance document on capillary Electrophoresis
The ICH Steering Committee recommends that the analytical procedures described in the official pharmacopoeial texts, Ph. Eur. 2.2.47. Capillary Electrophoresis, JP General Information. Capillary Electrophoresis, and USP General Information Chapter <1053> Biotechnology-derived Articles – Capillary Electrophoresis, can be used as interchangeable in the ICH regions. To view the guidance, CE FDA Guidance
Implementation of ISO/ISE 17025 by Agilent technoligies
To get the copy of Analytical instrument qualification from Agilent technologies click the link - Analytical Instrument Qualification
Guidance for UK Manufacturer’s Licence and Manufacturer’s Authorisation (for Investigational Medicinal Products) Holders on the use of UK Stand Alone Contract Laboratories
This document:
• Defines a stand alone contract laboratory in relation to quality control testing of medicinal products.
• Provides guidance as to when a contract laboratory must be named on a manufacturer’s licence for relevant medicinal products for human and veterinary use and/or a manufacturer’s authorisation for investigational medicinal products.
• Is applicable to all manufacturing licence holders, i.e. import, export, herbals and specials.
• Provides guidance as to when a contract laboratory is not required to be named on a manufacturer’s licence or authorisation.
• Outlines the MHRA’s criteria for inspection of contract laboratories.
This guidance can be downloaded by clicking Guidance .
A primer for Good laboratory Practice and Good Manufacturing Practice - For Analytical Laboratories
WHO good practice for pharmaceuticals quality control laboratory(draft)
Analytical Balance
NIST - weight and measurement-calibration procedure
NIST - Weight classification
A guide for Proper weighing of lab balance by Mettler
HPLC Column comparison
To find out alternative column for your column of interest.
HPLC Column comparison - USP Database
HPLC Troubleshooting guide
Instrument calibration
1. Disolution Apparatus 1 & 2 - Mechanical calibration
Procedure - FDA procedure - Dissolution - Mechanical calibration
Calibration of Dissolution Apparatus 1&2
Recently FDA has released a new guidance on Calibration of disolution apparatus 1 & 2. This guidance document more emphasis on enhanced mechanical calibration than chemical performance verification test. This guidance also recommends to manufacturer take appropriate control to handle recognised source of significant variablity during dissolution testing like dissolved gases, vibration and vessel dimensions. For more information go through the link .Guidance to industry -Dissolution
Dissolution procedure toolkit
USP released the version 2 of dissolution tool kit procedure for mechanical calibration and performance verification test apparatus 1 & 2. The dissolution toolkit provides a description of best practices associated with the mechanical calibration and performance verification test for the USP basket and paddle dissolution apparatuses and test assemblies.This second version of the dissolution toolkit represents a continuing effort to provide detailed information describing the procedures that if used will assure a properly qualified dissolution test assembly. For more information click Disolution Toolkit Procedure Version-2.
To refer version-1 click Dissolution Toolkit version-1
Further USP established a new acceptance criteria for current lot of Prednisone tablet. For more information click the link Performance of Equipment to Test Dissolution of Medications Further Assured
2. Prednisone tablet for PVT - New lot - P1I303
Prednisone Tablet for PVT - New lot released on March 2010
Prednisone Tablet for PVT - A new lot is released on March 01, 2010 Lot No.P1I300 valid through Feb 29, 2012 with test procedure an optional two stage test and calculation example. On April 30, 2010, Lot P0E203 will no longer be official.
Note: There was an error in the initial USP certificate dated Feb.22, 2010. It is now corrected. For corrected certificate click Prednisone Tablet for PVT - New lot released on March 2010.
Instrument Qualification
Qualification of Equipment (Core document)
Annex 1: Qualification of HPLC Equipment
Annex 2: Qualification of GC Equipment
Annex 3: Qualification of UV-Visible Spectrophotometers
Annex 4: Qualification of IR Spectrophotometers
Annex 5: Qualification of Automatic Titrators
NEW: Annex 6: Qualification of piston pipettes
Result & Reports
Evaluation & Reporting of Results
Concept paper on Storage Conditions during Transport
This paper is concerned with challenges related to the maintenance of appropriate transit conditions during transport as products move through all stages of the manufacturing and wholesale distribution system from active substance through the wholesale distribution system to ensure that patients and animals receive safe and efficacious medicinal products.
From a product’s perspective, transport is a mobile form of storage but where there are weaker controls than storage in fixed sites – therefore similar levels of controls should exist. Compliance at all stages of manufacture and distribution becomes more important as the number of transport stages increase, including transport (i.e. import) into the EU. Several examples have been seen where sea-freight significantly exceeds 30 days. Any increases in the length of time and/or the climactic challenge at each stage will also impact on compliance. It is also increasingly difficult to be aware of and to assess the cumulative effects of adverse incidents at different stages.
Many sites of manufacture are now located in tropical zones and/or where transport infrastructure may be difficult. Therefore the challenges arising from transport between such sites and from these sites to the EU may take finished products, or their earlier stages of manufacture, outside of the conditions defined in the EU Marketing Authorisation for storage of the product. Also, the risk of freezing during transport and the effects on the products should be considered.
It is important to understand the susceptibility of different products at the different stages and whilst the principles of quality risk management would be applied on a product by product basis at each stage of manufacture and transport would be expected, the reality is that different products and different product stages are frequently co-shipped. It is therefore evident that a simple set of readily understood general rules should apply to transit conditions to reduce this complexity and risk of error.
Although widely acknowledged, there is no explicit requirement for the need to conduct transport studies under worst case conditions and no requirement for routine monitoring during transport.
Primer for GLP & GMP for Analytical Lab - Agilent
Top ten deficiencies found during first assessment of new applications from October to December 2009 - EDQM
This document is a summary of the main questions resulting from the first assessment of new applications for Certificates of Suitability (CEP) for chemical purity. It is based on the content of 108 deficiency letters sent to the applicants on applications treated from October to December 2009.
The Top 10 questions are listed below with additional recommendations regarding EDQM requirements added. By including these recommendations - together with the requirements described in the EDQM Guideline "Content of the dossier for chemical purity" PA/PH/CEP (04) 1 (current version) which is available on our website - applicants can improve the quality of their dossiers with a view to facilitating and speeding up the granting of their CEP.
TOP 1 (3.2.S.2.2) / (3.2.S.2.3): Redefinition of starting material
TOP 2 (3.2.S.2.3): Absence of discussion on the carry-over of impurities/by-products from key materials
TOP 3 (3.2.S.2.3): Absence of discussion for Class 1 solvent as contaminant of another solvent
TOP 4 (3.2.S.3.2): Genotoxic impurities
TOP 5 (3.2.S.4.4): Absence of comparison of the quality of the final substance obtained with starting materials from different suppliers
TOP 6 (3.2.S.2.3): Incomplete specifications for the declared starting materials
TOP 7 (3.2.S.4.3): Suitability of the monograph to control the impurity profile of the final substance
TOP 8 (3.2.S.6): Specification for container closure system
TOP 9 (3.2.S.3.2): Compliance with the requirements of the Ph. Eur General Monograph 2034: limit for unspecified impurities
TOP 10 (3.2.S.2.3): Solvent recovery
For more information click the weblink
http://www.edqm.eu/medias/fichiers/PAPHCEP_10_65_Top_Ten_Deficiencies_New_Application.pdf
How to do document - New revised APIC guide - GMP for API
It describes the intrepretation of ICH Q7 with revision in quality management, personnel & agents,brokers,traders,distributors,repackers and relabellers - Version 6.
How to do document-Intrepretation of ICH Q7 -Verison 6 -Revised
Example of Quality Risk Management (QRM) Implementation by PIC/S
An informal working group within PIC/S has developed an example of methodology for the implementation of Quality Risk Management (QRM) in industry. For download example
EU GMP Guide chapter-7 revised - Outsourced activities -contract manufacturer and analysis
Chapter 7 of the EU GMP Guide "Contract Manufacture and Analysis" has been revised and was published on the GMP-information site of the European Commission on 9 November 2010.
Reasons for changes: in view of the ICH Q10 guideline on the Pharmaceutical Quality System, Chapter 7 of the GMP Guide has been revised in order to provide updated guidance on outsourced GMP regulated activities beyond the current scope of contract manufacture and analysis operations. The title of the Chapter has been changed to reflect this.
WHO guideline on Quality Risk Management
This guideline will align with the general framework described within other current international papers on this subject.
Principles of quality risk management- Four primary principles of QRM are:
•the evaluation of the risk to quality should be based on scientific knowledge and
ultimately link to the protection of the patient;
• QRM should be dynamic, iterative and responsive to change;
• the level of effort, formality and documentation of the QRM process should be
commensurate with the level of risk; and
• the capability for continual improvement and enhancement should be embedded in the QRM process.
Change in ICH classification of residual solvent - Cumene(Isopropyl Benzene) - From class 3 to class 2
Cumene is listed in the ICH Q3C(R4) guideline in class 3. A revision to the ICH Q3C(R4) guideline is proposed in which it is recommended that cumene be placed into class 2 to take account of new toxicity data.
To go through draft guideline and send comment click Draft guideline
Out-Of-Specification (OOS)
Investigation is must for any product failures to find out the root cause and Corrective And Preventive Action(CAPA). USFDA come up with definite guidance on this subject. This guideline helps to handle OOS data and procedure for investigation. For more information refer the below link. FDA Guidance - OOS
Out-Of-Trend(OOT) Analytical Results
OOT means an analytical result which fall with in the specification limit but does not follow with in the trend or unexpected result. Normally any analytical result which fall in Out-Of-Specification requires a detailed investigation to find a root cause failure and folowed by a currettive And Preventive Action(CAPA).
Though regulation demands investigation to be completed with in thirty days but most of the cases industries fails to complete the investigation with in stipulated period to find root cause. Meanwhile its end up with few more failures. To avoid such things happen the current practice starts investigation when results appear to be out-of-trend.
The following links help to know more about OOT
Identification of OOT-Stability results
Identification of OOT-Stability results-part-2
Revised Annex 13 on Investigational Medicinal Products (IMP) coming into operation
The European Commission has published on the EudraLex - Volume 4 webpage the new Annex 13 (Investigational Medicinal Products) of the EU Guidelines to Good Manufacturing Practice. The new Annex is coming into force in July 2010.
http://ec.europa.eu/health/documents/eudralex/vol-4/index_en.htm
Part 2 EU GMP Guide on APIs Will No Longer Be Identical to ICH Q7
The European Commission published a revised Part 2 text on GMP for APIs which will enter into force by 31 July 2010.
http://ec.europa.eu/health/files/eudralex/vol-4/2007_09_gmp_part2_en.pdf
A template for API quality agreement
This Quality Agreement template was developed by the Bulk Pharmaceutical Task Force (BPTF), an affiliate organization of the Society of Chemical Manufacturers and Affiliates (SOCMA), as a guide for drafting a Quality Agreement relating to the manufacture and release of substances regulated by the Food and Drug Administration. The template is based on the collective experience of industry members. This can be downloaded by clicking Quality agreement template
WHO released draft guidance for production and control of specified starting material
Specified starting material means any substance which is primarily or mainly used as a starting material for the production of an API, but which could be used directly as an API.
This guideline is intended to assist applicants or MA holders in assessing the required level of quality of “specified starting materials” that will be used for the manufacture of an API. It is also intended to help API master file holders (APIMF) in the compilation of their APIMFs
The control of the “specified starting materials” should be designed to detect isomeric or other impurities which are potentially reactive and could be carried through to the final product of the synthesis.
For more information click WHO guideline
Verification of Compendial Procedures - Changes Planned in the USP General Chapter <1226> -USP 35
In the Pharmacopeial Forum from November/December 2010, the USP proposed to revise the General Chapter <1226> Verification of Compendial Methods.
Changes planned are as below. USP planning to implement in USP 35.
-
The word "method" should be replaced by "procedure"
-
Aims to clarify the purpose and the scope of the verification process. "The verification process for compendial test procedures is the assessment of whether the procedure can be used for its intended purpose, under the actual conditions of use for a specified drug substance and/or drug product matrix."
-
"The process of assessing the suitability of a compendial analytical test procedure under the conditions of actual use may or may not require actual laboratory performance of each analytical performance characteristic."
The following will be added to the points which must be taken into consideration for the Verification of Compendial Procedures:
-
drug substance's synthetic route
-
method of manufacture for the drug product
-
effect of the matrix on the recovery of impurities
-
suitability of chromatographic conditions and column
-
appropriateness of detector signal response
The revision of the General Chapter <1226> Verification of Compendial Procedures should be published in the USP 35.
Clarification not provided by USP is "Whether the laboratory needs to prove the performance of each validation parameter for the assessment is left open".
Analytical Method Validation
Primer for validation of analytical method - Agilent technoligies
Validated analytical method only can give accurate results. Validation of analytical method is must for pharmaceutical analytical laboratory.
There is guideline for analytical method validation from ICH & US FDA.
ICH-Q2(R1)- Validation of Analytical Procedures - Text and Methodology
http://www.ich.org/LOB/media/MEDIA417.pdf
US FDA draft guidance on analytical procedures & method validation
FDA-Analytical method validation
EDQM guideline
EDQM-Validation of analytical procedure
Method validation - Particle size - Laser diffraction - Malvern application note New
Analytical Method Transfer
There is no definite guidance from USFDA on this subject. Recently USP has come up with a stimuli article on this subject. For more information refer the link below.
Transfer of analytical procedures-A new general information chapter
http://www.usp.org/pdf/EN/USPNF/PF35(5)_StimArticle-2.pdf
WHO draft guideline - Refer page 14
An article on analytical method transfer
Challenges in analytical method transfer
Auditing pharmaceuticals quality control Laboratory
Auditing quality control laboratory is must for continuous improvement and regualotory requirements. It helps to keep QC laboratory in high compliance level and maintain best practices through continuos improvement by training and gap analysis.
There is a guideline from US FDA for inspection pharmaceuticals QC laboratory it includes chemical lab and Micro lab.
Pharmaceutical Quality Control Labs
Guide to inspection of pharmaceuticals quality control laboratory
Audit check list for Pharmaceutical Quality Control Labs by PICScheme
inspection-of-quality-control-laboratories.pdf
Microbiological Pharmaceutical Quality Control Labs
Guide to inspection of microbiological pharamaceuticals quality control lab
Auditing Guide from APIC
World Health Organization Public Inspection Reports (WHOPIR)
The World Health Organization Public Inspection Reports (WHOPIR) is a summary of the inspection report of
-
a manufacturing site for Active Pharmaceutical Ingredients (APIs);
-
a manufacturing site for Finished Products (FPs);
-
an organization such as a Contract Research Organization where a bioequivalence study or other clinical study had been performed (CROs);
-
a quality control laboratory
The WHOPIR reflects the inspection report and gives a summary of the observations and findings made during the inspection, but excludes confidential proprietary information. It indicates also the date and duration of the inspection as well as the scope of the inspection.
The reported inspection reports are from India & china companies. Few examples are Ranbaxy, Cipla, Matrix, Lupin, IPCA, Aurobindo, Sitec lab,Vimta lab etc
To view/read the WHO inspection report click WHO inspection reports
Microbiology
Harmonization of microbial limit test - pharmtech
Objectionable microorganism Vs Specified microorganism
USP revised the general chapter <85> Bacterial Endotoxins Test
- Basic GMP Basic training module | WHO |
- Supplementary training module | WHO |
- Training and guidance | IPCS |
Wednesday, June 8, 2011
cGMP News
01.06.2011
In Vitro Test Methods for Detection and Quantification of Botulinum Neurotoxins and Detection of Non-Endotoxin Pyrogens
On 23 May the US Health and Human Services Department published a notice in the Federal Register which includes nomination of In Vitro Test Methods for Detection and Quantification of Botulinum Neurotoxins and Detection of Non-Endotoxin Pyrogens; Data Request for Substances Evaluated by these Test Methods. More details can be found here.
01.06.2011
The Council of the European Union adopts Falsified Medicines Directive! Major challenges for Users and Producers of APIs and pharmaceutical Excipients to be expected
The Falsified Medicines Directive has been adopted by the Council of the European Union on 27 May 2011. It is now about to be published in the Official Journal of the European Union within the next days. It contains substantial changes with respect to GMPs for APIs and pharmaceutical excipients. Please read here more about these new challenges for the API and pharmaceutical industry.
01.06.2011
EMA Report on Clinical Trials outside the EU
The European Medicines Agency (EMA) published a report from a workshop on ethics and GCP in clinical trials outside the European Union. Read more.
25.05.2011
The 4th European GMP Conference a great Success - Read more about major GMP Developments
From May 20-21, 2011 the 4th European GMP Conference was held in Heidelberg. The Conference attracted delegates from 25 different countries. The conference was booked up! Read more about the highlights.
25.05.2011
FDA publishes annual Fatalities Report regarding Blood Collection and Transfusion
The US FDA published their fatalities report of blood collection and transfusion for the fiscal year 2010. More details about the report and the comparison with former reports can be found here.
25.05.2011
The Challenges of Ensuring Laboratory Data Integrity
The integrity of laboratory data generated in analytical labs needs to be ensured for paper systems, for paper and electronic systems (hybrid), as well as for electronic systems. The problem is that "raw data" has not been defined in the new EU GMP Chapter 4. Please find in Dr. Bob McDowall's article how the definition of "raw data" in the GLP regulations can help.
18.05.2011
Suspension and Withdrawal of CEPs by EDQM
The EDQM announced on May 17, 2011 the availability of the revised policy document 'Suspension or Withdrawal of a Certificate of Suitability'. The EDQM also annouced information about new CEP suspensions and withdrawals due to failures to comply with the GMP requirements. Read more here.
18.05.2011
New Annex 14: Consequences for QPs
The EU has revised Annex 14 of the EU GMP Guide, defining requirements for drugs derived from human blood or plasma. In this context, requirements for the respective Qualified Persons have been updated. Read more.
18.05.2011
FDA asks how to improve existing Regulations
The US Food & Drug Administration (FDA) announced that the agency is formally asking for submissions on how to improve existing regulations. Read more.
11.05.2011
EMA: Monitoring of Products originating from Japan for the Possibility of Radioactivity
EMA is working with its European and international regulatory partners to monitor and evaluate the possible risk of radioactive contamination of medicines manufactured in Japan. Read more.
11.05.2011
Quality by Design for pharmaceutical Excipients - IPEC publishes new Checklists and Q&A Document
Three new documents published by the IPEC provide useful information for suppliers and users of APIs on Quality by Design at early stages of development. Read more here.
11.05.2011
EP 2.6.31. Microbiological Examination of herbal medicinal Products for oral Use under Revision
The EDQM announced the revision of the monograph 2.6.31. "Microbiological examination of herbal medicinal products for oral use" which specifies inspections for herbal drugs with particular specifications for Escherichia coli, salmonella and gram-negative bacteria with bile salt tolerance. More details can be found here.
11.05.2011
FDA's Strategic Priorities 2011 - 2015 now available
The U.S. FDA released the final version of a strategic priorities document outlining the goals that will guide the agency through 2015. Read more.
11.05.2011
EMA's answers to FAQ on Computerised Systems
The EMA (European Medicines Agency) has just published answers to questions on computerised systems under "Q&A: Good Manufacturing Practices (GMP)". Read more here.
04.05.2011
New PIC/S Document on GMP for APIs
A new document created by a PIC/S team of APIs experts raises the central issue related to the production and distribution of APIs and provides essential answers and clarification on the topic. Read more about the interesting collection of Questions and Answers here.
04.05.2011
CAPA among the most frequent GMP Deviations cited in FDA Warning Letters
As indicated by ECA's current Warning Letter Report, Production Record Review and respective CAPA deviations are (again) the most frequent GMP observations made by the FDA. Read more.
28.04.2011
Nuclear Load of pharmaceutical Products from Japan
Both ECA and Concept Heidelberg increasingly receive requests on whether a pharmaceutical manufacturer has to check substances and medicinal products from Japan for nuclear loads. Read more about the current situation.
28.04.2011
Revision of Chapter 8 of the EC guide to GMP
EMA's GMDP Inspectors Working Group has agreed on a concept paper on revising chapter 8 'Complaints and Product Recall' of the EC guide. Chapter 8 should introduce Quality Risk Management principles and appropriate root cause analysis work when investigating quality defects/complaints for both marketed products and IMPs. Read on here.
28.04.2011
EDQM's Enquiry on the new Draft of a general Chapter on Uniformity of Dosage Units
EDQM has published an enquiry on the draft concerning a new general chapter 2.9.47 - Demonstrating Uniformity of Dosage Units using Large Sample Sizes and an article on the topic on behalf of the PAT Working Group of the European Pharmacopeia. Read more here.
20.04.2011
Risk Management Principles used for WHO Inspections of API facilities
The new WHO Pharmaceutical Newsletter reports about the API inspection programme. This programme has been established by using risk management principles. Please read more here
20.04.2011
EDQM requires more Information on the Manufacturer's Localisation (DUNS/GPS) for CEPs
From 15 April, the European Directorate for the Quality of Medicines and Health Care (EDQM) requires for applications or revisions of a Certification of Suitability (CEP) the indication of the manufacturing site localisation with GPS data or a DUNS number. This change is in line with the requirements laid down in the new EU Site Master File. Read more here
20.04.2011
New Guidance on Investigational Medicinal Products (IMPs) and Non Investigational Medicinal products (NIMPs)
The EU Commission has published a revision of the Guidance on Investigational Medicinal Products (IMPs) and Non investigational Medicinal Products (NIMPs). Read more.
20.04.2011
Note for Guidance on minimising the Risk of transmitting Animal Spongiform Encephalopathy Agents via human and veterinary Medicinal Products
Regarding the developments in research and sciences of TSE and the current data about BSE arround the world, the European Commission revised the "Note for guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products". Read more here.
13.04.2011
New Limit regarding unspecified Impurities for certain Substances - EDQM Updates respective CEPs
34 monographs of Ph. Eur 7.0 to 7.2 have been revised regarding the limit for unspecified impurities. Read more about the consequences for applicants of new CEPs.
13.04.2011
New answers published about Variations: EMA's updated "Post-Authorisation" Guideline
The compilation of EMA's Questions & Answers on Variations has been recently updated. Additionally, a Procedural Guideline has been published. Read more about the new developments here.
13.04.2011
Quality IWG Training Material on ICH Q8, Q9 and Q10
The Quality Implementation Working Group has developed a consolidated training package on ICH Q8, Q9 and Q10 that is now available on the ICH website. Read more.
06.04.2011
May unvalidated Methods also be accepted to test Drug Products? - The FDA answers
The use of validated analytical test methods in GMP regulated laboratories is obligatory. Nevertheless, under certain circumstances exceptions may be allowed. Here you can read FDA's answer to the question asked in the title of this news.
06.04.2011
New EMA Checklist should help Type IA Variation Submissions
The EMA has published a checklist which is supposed to help applicants to check the correctness and completeness of type IA variation notifications. This will be certainly a precious help for those who have to compile documents under time pressure. Read more here.
06.04.2011
EMA and FDA announce Pilot Program for Assessment of QbD Applications
EMA and FDA are launching a three-year pilot program that will allow parallel evaluation of relevant quality data components, known as Quality by Design (QbD), of selected applications that are submitted to both agencies at the same time. Read more.
06.04.2011
Annual Product Review (APR) as GMP Deviation in FDA Warning Letters
Reviewing FDA's Warning Letters of the last fiscal year reveals that the Annual Product Review (APR) is still a hot topic. The main reasons can be found in failing timely completion and in inadequate processes. Read more.
30.03.2011
Video Presentation from FDA´s Dr Moheb Nasr available
A presentation from Dr Moheb Nasr about FDA´s Pharmaceutical Quality Initiatives was videotaped at the 13th European API Conference in Barcelona. Click here to read more.
30.03.2011
Dedicated Facilities: FDA publishes Draft Guideline
In March 2011, the Food and Drug Administration (FDA) published a new draft guideline which extends the requirements on the separation of penicillin also on other beta lactam antibiotics. Read more here.
30.03.2011
News IPEC-Americas "Distributors Audit Guide" for Pharmaceutical Excipients
IPEC Americas has published a new Distributors Audit Guide. The document was developped to support audits of API suppliers and their supply chain. European standards from the "Good Distribution Practices" and from the WHO were taken over. Read more here
30.03.2011
New Compilation of Community Procedures on Inspections and Exchange of Information
EMA has updated the Compilation of Community Procedures on Inspections and Exchange of Information, a tool for facilitating co-operation between the GMP inspectorates of the EU Member States. Read more.
30.03.2011
Production of WFI through Membrane Processes: Survey Results
Through a survey we asked the GMP Newsletter readers whether a change of the European Pharmacopoeia concerning the approval of membrane processes for the production of WFI would be interesting. You can find the results of the survey here.
25.03.2011
Results of Survey on EU GMP Guide Revisions of Chapter 5 (Production) and 7 (Contract Manufacture and Analysis)
At the end of last year, drafts about the changes of Chapter 7 (Contract Manufacture and Analysis) and Chapter 5 (Production) of the EU GMP Guide have been published. With regard of these changes, the European Compliance Academy (ECA) conducted a survey. The results were sent to the EMA too and - maybe - influence the final versions. Read more about the results of the survey here
25.03.2011
FDA Warning Letter Statistics 2010 regarding Process Validation and Qualification
In Warning Letter evaluation, the topic of process validation/qualification is not frequently observed since it is not an independent item of the cGMP Guide (21 CFR 210/211). In the following, you will find an evaluation of the Warning Letters 2010 on GMP deviations in regard to process validation and qualification in the manufacturing environment. Read more here.
25.03.2011
Requirements on Validation of Sterilisation Procedures according to ISO 17665-1
Qualification of a steriliser and validation of sterilisation procedures are essential GMP requirements for the manufacture of sterile medicinal products. Requirements on these topics can be found in the pharmacopoeia and in Annex 1 of the EU GMP Guide. However, there are no further executive regulations. In case of sterilisation procedure using moist heat, the EN ISO 17655-1 standard can be helpful. Read more here.
25.03.2011
Surveillance of Medicinal Products- Annual Report of the German Federal States
In February, the German Central Authority of the Federal States for Health Protection with regard to Medicinal Products and Medical Devices (ZLG) published its annual report on inspections. Read more here.
16.03.2011
China's new GMP Regulation effective since March 1, 2011
The State Food and Drug Administration of China (SFDA) published a revised version of the GMP regulation. This new version came into force just recently, on 1st March 2011. Read more here.
16.03.2011
Amended Directive 2001/83/EC includes stronger Guidance on GMP for APIs and Excipients
The amendmends to the directive 2001/83/EC regarding the prevention of the entry of falsified medicinal products into the legal supply chain were adopted by the EU Parliament on 15 February. These amendments will affect many central fields of drugs manufacturing. As a consequence, the GMP regulations for pharmaceutical APIs and exicpients are going to be tightened. Read more.
16.03.2011
FDA: Applications to contain Information described by ICH Q8
As part of its Manual of Policies and Procedures, FDA's CDER has published a document called "Applying ICH Q8(R2), Q9, and Q10 Principles to CMC Review". Read more about the expectations.
16.03.2011
EMA plans on focusing more on API Manufacturers located in Asia
The EMA reacts on the fact that the manufacturing of APIs is moving to areas outside the EU, especially to Asia (mainly China and India). Read more here.
16.03.2011
FDA focuses more on Supplier Qualification
Compliance of suppliers and the challenges in all stages of purchasing, manufacturing and distribution is getting more and more in the focus of inspectorates. Read more.
09.03.2011
New FDA Guidance Documents in Calendar Year 2011
On January 26, 2011 the FDA issued the Guidance Agenda: New & Revised Draft Guidances CDER plans on publishing during the calendar year 2011. Click here to read more.
09.03.2011
Evaluation of the Warning Letters issued by the FDA for the Fiscal Year 2010 with regard to Risk Management
What do inspectors have to object to in regard to Quality Risk Management? Read more here.
09.03.2011
Quality Agreement templates for every Participant of the 4th European GMP-Conference
All delegates of the 4th European GMP Conference on 19/20 May 2011 in Heidelberg will receive sample contracts on quality agreements for contract manufacturing, for contract analytics, for... Read more here.
09.03.2011
FDA and EMA Pilot Program for joint Review of QbD Components of new Drug Marketing Applications
The Food & Drug Administration (FDA) and the European Medicines Agency (EMA) will launch a collaborative Quality by Design (QbD) Application Review Pilot. Read more.
09.03.2011
EMA plans extensive Revision of the EU GMP Guide
At the beginning at this year, the European Medicines Agency (EMA) published the Work Plan for GMP/GDP (Good Manufacturing Practice/Good Distribution Practice) Inspectors Working Group. This document provides a good overview of the changes upcoming in the GMP/GDP environment - and it might come to a lot of changes. Read more here.
03.03.2011
Inspection of API manufacturers: First Results of the WHO Pre-Qualification Programme
Within the framework of its pre-qualification programme of APIs, the WHO has published detailed results about the inspections performed at API manufacturing sites. Information about the GMP deviations found as well as further interesting facts can be found here.
03.03.2011
"Impurities: Guideline for Residual Solvents Q3C(R5)" has been finalised
Because of recent investigations on toxicity of Isopropylbenzene (Cumene), there was a need to assign this solvent to the higher Class. Consequently, the ICH Guideline Q3C(R4) had to be revised once more. The final document is now available. You can find out more here.
03.03.2011
Aide memoire of German Inspectors now also available in English
All the participants of the 4th European GMP Conference scheduled in Heidelberg on 19/20 May 2011 will receive the English version of the inspectors' guide (Aide memoire) on Qualification/Validation. Read more here.
03.03.2011
Validation on Rank 3 in the FDA Warning Letter Statistic 2010 regarding Medical Devices
Concept Heidelberg regularly analyses the Warning Letters issued by the FDA. In the following, you will find a ranking based on the evolution of the Top 5 deviations in the FDA Warning Letters (regarding Medica Devices) issued between the years 2002 and 2010. On place 1 is … Read more here.
03.03.2011
Batch Record Review as GMP Deviation cited in FDA Warning Letters
As indicated by ECA's Warning Letter Report, Production Record Review deviations are (again) the most frequent GMP observations made by the FDA. Read more.
01.03.2011
EMA adjusts Fees for Marketing Authorisation Applications
From 1 April 2011 the EMA will charge new fees for its services in relation with marketing authorisations of medicinal products. Yet, fee reductions will be applied for marketing authorisations of orphan drugs, when specific criteria are met. Read more here.
01.03.2011
ICH Q11 Draft Gelling On Lifecycle/Change Management and Control Strategy Components
The lifecycle management section of the newest working draft of ICH's Q11 guideline on drug substance development and manufacturing provides allowance for applicants to include change management proposals in their original submissions. Read one here.
01.03.2011
Concept Paper on the Revision of the GCP Directive published
The European Commission has published a Concept Paper on the revision of the GCP Directive 2001/20/EC. Both the contents of the directive and the transposition into national law now might be revised. Read more.
01.03.2011
IMPD: EMA provides further Clarification for Quality of IMPs
The European Medicines Agency EMA has published a set of new Questions and Answers regarding the quality of Investigational Medicinal Products (IMPs). Read more.
01.03.2011
Specific WHO Requirements for Dissolution Studies to Support Biowaivers
The requirements on dissolution testing and the main focuses of an inspection are at the core of the WHO document "Points to Consider for Inspections of Biowaiver Data". You can read more about this new WHO-Dokument here.
24.02.2011
Revision or Renewal of CEPs: Requirements for Notifications to the EDQM
The EDQM has to deal with an increasing number of deficiencies in the notifications regarding revisions or renewals of CEPs which makes the procedure inefficient and which could be easiliy avoided. Here you can read more about the most common deficiencies found in the documents submitted to the EDQM.
24.02.2011
EU-GMP Guide: New Introduction with Clarification of Status of Part III
As mentioned in a previous news, ICH Q9 and ICH Q10 will be adopted as Part III of the EU GMP Guide. In this regard, the EU Commission has revised the Introduction of the EU GMP Guide and clarified he status of the new Part III. Read more.
24.02.2011
"Q3D: Impurities: Guideline for Metal Impurities" - a new ICH Concept Paper
The control of residual solvents and organic impurities in drugs and APIs is "globally" regulated in respective ICH guidelines (resp. for the economic areas Europe, USA and Japan). For metal impurities there is no comparable harmonised document available, though. The ICH initiated the development of a new guideline in order to close this gap. Read more here.
24.02.2011
Guideline on Testing for the Detection of Mycoplasma Contamination of veterinary medicinal Products
The CVMP of the European Medicines Agency published the draft of VICH GL34: Guideline on testing for the detection of mycoplasma contamination for further consultation. More about the guideline can be found here.
24.02.2011
New EMA/HMPC Reflection Paper on Stability of Herbal Medicinal Products
The EMA/HMPC/3626/2009 Reflection Paper depicts the need for specific guidelines on Stability for herbal and traditional herbal medicinal products and presents the solution which is agreed on. Click here to get more information.
24.02.2011
DMA Document on Expectations for Audits of API Manufacturers
The Danish Medicines Agency (DMA) has published a document entitled: The Danish Medicines Agency's expectations for audits of API manufacturers. The DMA defined a number of expectations which need to be fulfilled if the QP delegates the task to a third party. Read more here.
22.02.2011
Updated Q&A Document on the Submission of Variations published
The CMDh updates irregularly a Q&A document about the difficulties concerning the submission of variations applications and the classification of changes according to the new "Variations Regulation" (EC) 1234/2008. An updated Q&A document has been recently published. Read more here
22.02.2011
EDQM develops Live Demo for a Track & Trace System
The EDQM, which works on a Europe-wide Track & Trace system as part of its anti-counterfeiting strategy, has announced the creation of a live demo for Phase 2 of its project. Read more.
22.02.2011
EMA publishes final ‘Road map to 2015’
The European Medicines Agency has published its final 'Road map to 2015', setting out EMA's role as a public-health agency. Read more.
22.02.2011
New Pharmacovigilance Legislation adopted
Following the adoption by the Council and the European Parliament, a new Regulation and a new directive on pharmacovigilance were published in the Official Journal of the EU. Read more.
22.02.2011
Discussions about Material Certificates
The question around the material certificates needed for metallic products has long existed. Still, this topic is continuously being discussed. Read more.
22.02.2011
EMA/HMPC Reflection Paper on Extracts Purification
An EMA/HMPC Reflection Paper on the Level of Purification of Herbal Preparations to be considered as such has been published. Go here for more information.
22.02.2011
USP <85>Bacterial Endotoxin Test - proposed interim Revision Announcement
The USP proposed an interim revision of chapter <85> "Bacterial Endotoxin Test" based on a recommendation of the FDA and additions to the harmonised texts. Find out more here.
17.02.2011
In-depth analysis of the requirements on the new EU / PIC/S Site Master File
The new EU Site Master File document and the revision of the PIC/S document PE 008 on the creation of a Site Master File implies profound changes for the Site Master Files author. These changes affect every pharmaceutical manufacturer as a Site Master File is the basis for the inspection by a regulatory authority. You can find a detailed comparison between the new EU / PIC/S Site Master File document and the draft of the EC Commission here.
17.02.2011
FDA takes action against non-compliant manufacturer
On January 18, 2011 the US FDA obtained permanent injunction against Deltex Pharmaceuticals Inc. FDA has announced just recently that it will take immediate actions if manufacturers fail to comply with cGMP requirements. Read more here.
17.02.2011
The number of Warning Letters issued to Drug Companies and API Manufacturers increases
The number of Warning Letters the FDA issued to drug companies and API manufacturers last year has heavily increased. Some European companies are to be found among the addressees. A systematic analysis shows that most of the frequent deviations have been the same since four years. Read more here.
17.02.2011
FDA launches Basics for Industry Website
The U.S. FDA launched a new website called FDA Basics for Industry. On these web pages a lot of information is provided about the FDA, its responsibilities, expectations and regulatory processes. Read more.
17.02.2011
Quality of Herbal Medicinal Products - Current EMA/HMPC Q&A Document
A new EMA/HMPC document presents 26 different Questions and Answers on Quality of herbal medicinal products/traditional herbal medicinal products. Focus is on Testing Stability: 12 Questions and Answers are dedicated to that subject. You will find more information here.
17.02.2011
Results of the Survey "Implementation of the new Annex 1 requirements for Capping"
Concept Heidelberg started a European survey about the implementation of the requirements to Annex 1 for Vial Capping in 2010 . You can find the first results here.
16.02.2011
New Pharma Directive on Counterfeit Medicine adopted by EU Parliament
Yesterday the amendments on the Directive EC 2001/83/EC to combat counterfeit medicines (The Pharma Package) have been discussed in the European Parliament. Today, the EU Parliament adopted the amendments with an overwheling majority of votes.
The proposed amendments, which will have to be transferred into national law within two years include
- introduction of safety features (serial numbers and/or tamper-evident seals)
- more stringent rules for importation of APIs
- better controls of the supply chain (traders and wholesalers)
- Rules for the internet sale of medicines
- Harmonisation of GMP inspections
For further information please see the complete news.
10.02.2011
New version of EudraGMP allows access to information from all Member States
On 07. February 2011 the EMA announced a new version of the EudraGMP database. Click here to read more
10.02.2011
EMA publishes ICH Q9 and ICH Q 10 as Part 3 of the EU GMP Guide
The EMA announced the adoption of ICH Q9 and ICH Q10 as Part 3 of the EU GMP Guide. ICH Q9 was already published as Annex 20 but ICH Q 10 was not published as an Annex yet. Click here to read more.
10.02.2011
Growing Requirements on Process and Technology Transfers
Guidelines about Documentation on Transfers have been rather poor so far. Newly available GMP documents provide helpful information now. Read more.
10.02.2011
EMA publishes two documents on the QP Declaration concerning GMP Compliance of the API
The European Medicines Agency (EMA) has published two new draft documents for a template for the QP's declaration concerning GMP compliance of the API used as starting material and verification of its supply chain called "The QP declaration template". Read more.
10.02.2011
PIC/S SMF Guide Updated with Quality Management System Requirements
The PIC/S Committee has adopted the revision of the Explanatory Notes for Industry on the Preparation of a Site Master File The main purposes of the revision were the simplification of the document and the implementation of requirements in relation with Quality Management Systems (QMS). Read more.
02.02.2011
Detailed Analysis of FDA´s New Process Validation Guidance
Since November 2008 there is a draft for the revision of the old FDA Process Validation Guideline. On 25 January 2011 the FDA has published the final version of this new Process Validation Guidance. Read a detailed analysis here.
02.02.2011
Warning Letters Report 2010: Laboratory Controls and Analytical Methods again among Top Five GMP Deviations
The analysis of FDA's Warning Letters from fiscal year 2010 shows growing deviations in Laboratories. Unadapted analytical methods and missing documentation keep on increasing. Read more here.
02.02.2011
Clean Room Classification: Draft on ISO 14644 published
After the first documents on the planned changes of the ISO standard 14644 have already circulated in November, the official Draft version to comment is now available. Read more.
02.02.2011
News published about Guidance on Combating Counterfeit Drugs
The EU Commission, European Parliament and Council of Ministers met end of December to discuss the goal of finding an agreement on changing the EU Pharmaceutical Package Part 2 (Directive on Combating Counterfeit Drugs). Read more.
27.01.2011
FDA publishes Final of new Process Validation Guidance
Since November 2008 there has been a draft for the revision of the old FDA Process Validation Guideline. On 25 January 2011 the FDA published the final version of this new Process Validation Guidance. Read more here.
27.01.2011
The New GMP Annex 11 and Chapter 4 is Europe's Answer to Part 11
This month saw the publication of the new revision of European Union (EU) GMP Annex 11 on Computerised Systems and Chapter 4 on Documentation. The impact of these new revisions is extensive as combined they are the equivalent to the FDA's Part 11 regulation for electronic records and signatures. Read more.
27.01.2011
Laboratory Control Issues Prominent in Recent Warning Letters to Four Overseas Firms
Laboratory control problems are prominent in a bolus of FDA drug GMP warning letters recently issued to companies in Asia and Europe. Please read more about this development in a very detailed article provided by the IPQ - one of the most important Journals in the GMP and regulatory environment. Click here
27.01.2011
EDQM strengthens international Collaboration
The EDQM is strengthening its collaboration by signing Memorandums of Understanding (MoU) with the National Institute of Food and Drug Safety Evaluation (NIFDS), Korea Food and Drug Administration, and the Chinese National Institute of Food and Drug Control (NIFDC), respectively. Read more.
19.01.2011
New EU GMP Guide Chapter 4 on Documentation
The final Chapter 4 ("Documentation") of the EU Guideline to GMP has now been published and will come into operation on 30 June 2011. Some important changes were included. Get a summary here.
19.01.2011
Compliance Policy Guide: RFID Studies and Pilot Programs for Drugs
FDA is extending the expiration date of compliance policy guide (CPG) Sec. 400.210 entitled ‘‘Radiofrequency Identification (RFID) Feasibility Studies and Pilot Programs for Drugs’’ to December 31, 2012. Read more here.
19.01.2011
ICH Q8, Q9 und Q10: new Q&A Document published
The ICH Quality Implementation Working Group (Q-IWG) has issued volume 4 of the ICH guideline Q8, Q9 and Q10 - Questions and Answers Document. Read more.
12.01.2011
New FDA Guidance: Codevelopment of Investigational Drugs for Use in Combination
FDA's Center for Drug Evaluation and Research (CDER) has published a Guidance for Industry on the codevelopment of two or more novel drugs to be used in combination to treat a disease or condition. Read more.
12.01.2011
USP <1113> Microbial Identification - In Process Revision including a title change
The United States Pharmacopeia revises chapter <1113> about microbial characterisation, identification and strain typing including a change of chapters name. Read more here.
12.01.2011
New Best Practice Guides for the Submission and Processing of Variations published
The Co-ordination Group for Mutual Recognition and Decentralised Procedures - Human, CMD(h), has published the latest version of its Practice Guides for the Submission and Processing of Variations in the Mutual Recognition Procedure. Read more.
12.01.2011
FDA Inspections: Current Initiatives
The globalization of the pharmaceutical supply chain and the quality issues that have arisen because of that globalization, the FDA initiative "Pharmaceutical Quality for the 21st Century" and resource constraints that all Health Authorities are feeling are all changing the way FDA is viewing their mission to protect the American consumer. Click here to get an overview about the current initiatives.
05.01.2011
Complete Revision of USP Chapter <1116> including updated Cleanroom Classification
In the USP Pharmacopeial Forum Volume 36, No. 6, the chapter <1116> "Microbial Evaluation of Clean Rooms and other Controlled Environmentsis" has been published with the status "In-process-revision". Read here more about the proposed changes.
05.01.2011
FDA issues Guidance on Public Comment Procedures at Advisory Committee Meetings
The FDA has issued a final guidance for people who wish to comment during the agency’s advisory committee meetings. Read more.