Gruppo Ispezioni Fornitori

GIF (Inspections Suppliers Group) is a reality!
Want to know what the GIF and what benefits you receive?
Want to know why a pharmaceutical company should adhere to the GIF?
Want to know why a supplier benefits from joint inspections of GIF?

The GIF is a working group, formally established, comprising experts from various companies, with the purpose to create/develop synergistic activities between member companies in the pharmaceutical, chemical-pharmaceutical, food, nautraceutico, etc. on issues of quality and GMP, as well as promote innovation and ultimately help to produce those "savings" now more than ever necessary to ensure the development. The GIF is actually to fill in the national role played in Germany since the VFA (Verband Forschender Arzneimittelhersteller-Association of Research-based Pharmaceutical Companies) and Spain Auditorias the Forum, which have long since implemented the method of joint audits.


EMA QP declaration

The objective of this guidance and the Qualified Person (QP) declaration template is to emphasise the importance of providing a valid declaration, to harmonise the format for the declaration, to forestall questions during assessment, and to enhance the efficiency of the regulatory process, including the timely processing of relevant regulatory submissions.
Applicants are therefore strongly recommended to use the template to facilitate the validation of regulatory submissions and their review.
Guidance on the provision of the QP declaration is given in European Commission Guidelines of 16.05.2013 on the details of the various categories of variations.


MHRA GMP Data Integrity Definitions and Guidance for Industry January 2015

Data integrity is fundamental in a pharmaceutical quality system which ensures that medicines are of the required quality. This document provides MHRA guidance on GMP data integrity expectations for the pharmaceutical industry. This guidance is intended to complement existing EU GMP, and should be read in conjunction with national medicines legislation and the GMP standards published in Eudralex volume 4.
The data governance system should be integral to the pharmaceutical quality system described in EU GMP chapter 1. The effort and resource assigned to data governance should be commensurate with the risk to product quality, and should also be balanced with other quality assurance resource demands. As such, manufacturers and analytical laboratories are not expected to implement a forensic approach to data checking, but instead design and operate a system which provides an acceptable state of control based on the data integrity risk, and which is fully documented with supporting rationale.
Data integrity requirements apply equally to manual (paper) and electronic data. Manufacturers and analytical laboratories should be aware that reverting from automated / computerised to manual / paper-based systems will not in itself remove the need for data integrity controls. This may also constitute a failure to comply with Article 23 of Directive 2001/83/EC, which requires an authorisation holder to take account of scientific and technical progress and enable the medicinal product to be manufactured and checked by means of generally accepted scientific methods.
Throughout this guidance, associated definitions are shown as hyperlinks.


Warning Letters on Data Integrity: What does the FDA expect from Third Party Auditors and Consultants?

In some of the Warning Letters from fiscal year 2014 serious deviations with regard to the handling of electronic data (e.g. data manipulation) are listed. Typically, you can find in the Warning Letters the following statements:

  • Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to assure compliance with established specifications and standards (21 CFR 211.194(a)).
  • Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).
  • Your firm frequently performs “unofficial testing” of samples, disregards the results, and reports results from additional tests.
  • The inspection revealed your firm’s use of scratch paper containing critical manufacturing data. The data on these scratch paper records did not always match the data on the corresponding official batch records...

These quotations are taken from 4 Warning Letters which were all addressed to Indian pharmaceutical companies (please find here as an example a Warning Letter from February 2014). The GMP deviations detected during inspections with regard to electronic data are so elementary that the FDA urgently recommends to the companies concerned to occasionally get a Third Party Auditor who would first perform an in-depth GMP audit and then support the company remove the deficits with respect to data integrity. The consultants should be experts in this area.
In the Warning Letters mentioned, the FDA defines which services the consultant has to bring ("Your data integrity expert should..." ). These requirements are largely identical in the 4 Warning Letters and consist of the following measures:

  • Gapless identification of all time periods where electronic data have been recorded and documented incorrectly.
  • Identification and interview of all employees who were employed at the site before, during, or shortly after these time periods. Activities in connection with systems, procedures and behaviour of the management which contributed to or caused the GMP deviations while handling electronic data should be detected.
  • Employees who left the company before, during, or shortly after these time periods should also be interviewed accordingly.
  • Additional supporting indications of GMP non-compliant handling of electronic data should be identified. The involvement of other sites should be taken into consideration.
  • The managers in charge during the time periods in question have to be identified by means of organigrams and SOPs. It must be revealed to what extent the top and middle management knew about or was involved in the data manipulation.
  • The data integrity expert should find out whether managers who have been identified this way are still able to have an influence on the integrity of GMP relevant data (also with regard to applications for marketing authorisations). Internal reviews are to be extended to other sites which are known to be involved in violations of GMP-compliant handling of data.

For the auditor processing these points, the task is similar to detective work - which is likely to be demanding and not pleasant - as it may be doubtful that he or she gets the fullest support from the company concerned. Yet, this detective work is essential in the interests of patient safety and is taken very seriously by the FDA, especially with Indian companies as the Agency doesn't rely on their capability to resolve the data integrity problems without external support.


Linea Guida EU 19/03/2015 - GMP per gli eccipienti

E' stata pubblicata la Linea Guida Eu del 19 marzo 2015 sulla valutazione formale del rischio per accertare quali siano le buone prassi di fabbricazione appropriate per gli eccipienti dei medicinali per uso umano.


GDP Guidelines (API)

Il 19/03/2015 sono state pubblicate le linee guida EU sui principi di Buona Prassi di Distribuzione (GDP) dei principi attivi per i medicinali ad uso umano.





on Wednesday  16th of September 2015 at 2.00 p.m.


c/o AFI offices, Viale Ranzoni 1 Milano (Italy)



EU issues new Version of GMP Guide Chapters 3 and 5

The EU has re-published the recently revised Chapter 3 Premises and Equipment and Chapter 5 Production (we reported) and has made modifications regarding the transition period for the introduction of toxicological evaluations of products in multipurpose facilities. The two new documents carry the date 23 January 2015. The date of validity remains the 1 March 2015. The document now comprises a description of a stepwise procedure for the introduction of a risk management system to evaluate whether products need to be manufactured in dedicated or can be manufactured in multipurpose facilities. The procedure matches with that of the associated EMA "Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities". That means that starting with the 1 June 2015 the new requirements are valid for new products which are evaluated regarding the manufacture in dedicated or multipurpose facilities for the first time. For products already manufactured in multipurpose facilities the new regulations are valid from 1 December 2015.

Hence the EMA Guideline is now explicitly mentioned, even if only in footnote 1 of the new chapters. In the draft of the two chapters this reference was still included, in the final versions references to the EMA Guideline were completely omitted.


Importers of Medicinal Products

Concept Paper on new guidance for importers of medicinal products.

13 May 2015


GMP/GDM Inspectors Working Group


Data Integrity

Sono scaricabili l'articolo "Getting to the bottom of Data Integrity" di "The Journal, Issue 32, 2015" e la linea guida "MHRA GMP Data Integrity definitions and guidance for industry March 2015".


Aggiornamento dell'elenco dei Paesi terzi equivalenti per la produzione di API

DECISIONE DI ESECUZIONE UE 2015/1057 del 01/07/2015.

E' stato aggiornato l'elenco dei paesi terzi dotati di un quadro normativo applicabile alle sostanze attive per la fabbricazione di medicinali per uso umano e delle corrispondenti attività di controllo e di applicazione della Legge che assicurino un livello di tutela della salute pubblica equivalente a quello dell'Unione.

Per l'importazione di API da questi Paesi non è necessaria la Written Confirmation.


EMA - Medicines shortages

EMA, 21 December 2015.

"Developing a proactive approach to the prevention of medicines shortages due to manufacturing and quality problems."


Comunicato AIFA 24/02/2016


Sostituzioni di Persone Qualificate in applicazione dell’art. 50 del D. Lgs. 219/06 (24/02/2016)
Avviso alle Aziende Farmaceutiche

Si comunica che l’art. 50, c. 5 del D. Lgs 219/06 prevede che per ogni modifica delle condizioni essenziali in base alle quali è stata rilasciata l’autorizzazione alla produzione di medicinali o di sostanze attive soggette a regime di autorizzazione, le Aziende presentino apposita istanza  all’AIFA che provvede ad emettere la relativa autorizzazione.
La sostituzione della Persona Qualificata rientra nella casistica delle modifiche essenziali per le quali le Aziende sono tenute a presentare specifica istanza e ad attendere che l’AIFA si pronunci sulla stessa. Tale sostituzione decorre dalla data di emissione dell’autorizzazione da parte dell’Ufficio Autorizzazioni Officine.
Qualora la modifica sia generata dall’improvvisa necessità di sostituire la Persona Qualificata, la nuova Persona Qualificata può svolgere la propria funzione in attesa che l’AIFA autorizzi formalmente tale sostituzione (art. 50, c. 6), con nuova autorizzazione, solo se l’improvvisa necessità è tempestivamente comunicata e debitamente documentata ai fini dell’applicazione del comma 6 dell’art.50.
La nuova autorizzazione decorrerà dalla data nella quale è stata comunicata l’inizio dell’attività da parte della nuova Persona Qualificata, per l’improvvisa necessità di sostituzione.
Ove non sia applicabile il comma 6 dell’art. 50, la nuova Persona Qualificata è autorizzata a svolgere le proprie funzioni solo dopo formale autorizzazione da parte dell’AIFA.


Quality Working Party questions and answers on API Mix.

12/04/2016 - Q&A about mixture of API and excipients.


MHRA GMP Inspections

MHRA GMP INSPECTIONS - Deficiency data trend 2015.

E' scaricabile dal sito il documento del MHRA che riassume i risultati delle ispezioni GMP fatte dall'Autorità Regolatoria inglese nel 2015.


FDA: GMP for combination products

FDA Guidance for Industry: GMP requirements for combinantion products.

Gennaio 2017

La linea guida FDA riassume i requisiti GMP da applicare ai prodotti costituiti dalla combinazione di medicinali, dispositivi o prodotti biologici.


APIC - Guide for auditing