Indian API Manufacturers remain in the Focus of European GMP Inspectors

Some time ago three Non-Compliance Reports have been published in quick succession in the EudraGMDP database. Those reports deal with inspections performed at pharmaceutical APIs production sites located in India. Read more about the fundamental violations of the requirements for GMP-compliant API manufacturing in those facilities.,15332,S-WKS_n.html

The EudraGMDP database contains more and more frequently Non-Compliance Reports of API facilities located in India. Three of these reports were published in April and May this year. The companies inspected (Krebs Biochemicals & Industries Ltd, J P Laboratories Private Ltd and Dhanuka Laboratories Ltd) were accused of major violations of the GMP rules (in one case even a critical violation was observed). All in all, the GMP inspectors came to the conclusion that – in their current states – those facilities are not able to manufacture APIs in a GMP-compliant way.

At all three companies, deficiencies against the fundamental requirements for GMP-compliant manufacturing and testing of pharmaceutical APIs were identified – like for example:

  • Poor deviation management and change control
  • Insufficient storage and handling of starting materials, intermediates and finished products with risks of mix-up
  • Technical building defects favouring cross-contaminations
  • Use of non-qualified equipment in production and quality control
  • Inadequate management of electronic documents and data integrity not guaranteed

One critic – which is not specific to those cases but common to many other Non-Compliance Reports regarding facilities in the Far East – refers to inadequate personnel training and their lack of GMP understanding. In two cases, the EDQM has already withdrawn the CEPs for the APIs; in the third case which is currently being examined by the EDQM, a suspension of the CEP seems to be only a matter of time.


The Italian National Competent Authority which inspected the companies Krebs and J P Laboratories recommends the prohibition of supply, whereas the Authority of Croatia which inspected the facility Dhanuka even recommends the withdrawal of the GMP certificate as well as the removal from the corresponding marketing authorisation dossier.

Source: EudraGMDP Database


//////////European GMP Inspectors, Indian API Manufacturers, Krebs Biochemicals & Industries Ltd, J P Laboratories Private Ltd and Dhanuka Laboratories Ltd


Revision of the general Chapter on Pharmaceutical Water in the US Pharmacopoeia

The 2nd supplement of USP39 NF34 comprises the revised version of the chapter on pharmaceutical water of the US Pharmacopoeia <1231> Water for pharmaceutical purposes.,15266,15221,15612,Z-PEM_n.html

The 2nd supplement of USP39 NF34 comprises the revised version of the chapter on pharmaceutical water of the US Pharmacopoeia <1231> Water for pharmaceutical purposes. The first draft version had already been published in September 2015 in the USP Pharmacopeial Forum 41(5).

First of all: there are no new or revised specifications of individual test parameters or new requirements. But the chapter has been revised structurally to ensure better readability. In addition there are now also details regarding feed water as well as for the validation and on action and warning limits. With a chapter number greater than 1000 the Chapter <1231> is not binding, but has a recommending character. The recommended temperature for hot sanitising was changed. So far temperatures of 80 ° C and greater were recommended. Now these are 65-80 ° C. Regarding the action and warning limits the USP now comprises proposals how these can be set 2 – and 3-stepped and which rationale can be used for the limit-setting. Further, the revised chapter now also provides assistance for organising sampling plans for the validation and operational phases.

The revised version of the Chapter <1231> will become effective in December 2016 and can be found in the 2nd supplement to the USP39 NF34.


Final WHO Guidance Document on Good Data and Record Management Practices

The WHO has just released the  the final version of the important guideline “Good Data and Record Management Practices“.,15637,Z-COVM_n.html

We recently informed you about the WHO Draft Guidance on Good Data and Record Management Practices. Now, the WHO has just released the  the final version of this important guideline “Good Data and Record Management Practices”.

The final version is sectioned rather similar to the draft version:

– Introduction
– Aims and objectives of this guidance
– Glossary
– Principles
– Quality risk management to ensure good data management
– Management governance and quality audits
– Contracted organizations, suppliers and service providers
– Training in good data and record management
– Good documentation practices
– Designing and validation systems to assure data quality and reliability
– Managing data and records throughout  the data lifecycle
– Addressing data reliability issues
– References and further reading

Although the individual chapters were kept rather unchained the content of these chapters was updated throughout the whole document.

For instance the term “good documentation practices” has now been expanded to “good data and record management practices” and is defined as follows in the glossary:

“The totality of organized measures that should be in place to collectively and individually ensure that data and records are secure, attributable, legible, traceable, permanent, contemporaneously recorded, original and accurate and that if not robustly implemented can impact on data reliability and completeness and undermine the robustness of decision-making based upon those data records.”

Some of the former content has been put into Appendix 1 now: Here you can find expectations and examples of special risk management considerations for the implementation of ALCOA (-plus) principles in paper-based and electronic systems. The tables in this appendix provide further guidance on the implementation of the general ALCOA requirements. In addition, examples of special risk management considerations as well as several illustrative examples are provided of how these measures are typically implemented.

However, these examples should not be taken as setting new normative requirements.

For further information please see the final WHO Guidance on Good Data and Record Management Practices.

//////Final , WHO Guidance Document,  Good Data and Record Management Practices