[Stability Testing related News – vol.31]

◆  How to prepare for a Data Integrity Inspection (16-Aug-17 ECA)

Data governance and integrity have been getting more and more in the focus of regulatory inspections. But companies can prepare for these inspections. In the following you will find out how this can be accomplished with planned and periodic internal audits to ensure that compliance and performance are sustained and enable corrective actions to be taken at an early stage.

The ALCOA principle

The acronym ALCOA is used as a framework for ensuring data integrity and governance. ALCOA relates to data, whether paper or electronic, and is defined as Attributable, Legible, Contemporaneous, Original and Accurate:

• Attributable – who performed an action and when
• Legible – can you read a data file or all written entries
• Contemporaneous – documented at the time of the activity
• Original – written printout or observation or a certified copy
• Accurate – no errors or editing without documented amendments

This should be the basis for all your data governance activities and leads the way to control the integrity of your data.

What to look for

When you evaluate your systems to check whether compliance is met, you should consider the following aspects:

• Is all the data and meta data complete (how do you define data and how is data collected)?
• How is the data processed (how do you make sure that data is not changed or even falsified)?
• How is the data reviewed (what is reviewed and to what extent)?
• How is data summarised and reported (how do you make sure that all relevant data is used and data selection is prevented)?
• How do you retain and archive the data (what, how and where)?
• Are all processes and interfaces validated?

What helps the auditor through all the data?

A systematic approach should be chosen and an auditor should:

• Review applicable SOPs
• Review or create flow charts and process maps
• Identify critical steps
• Identify critical interfaces
• Identify critical documentation
• And, not to forget, review of previous internal and external audit findings with corrective actions and their effectiveness

In detail, as an auditor, you should have a look at data entries and perform plausibility checks for various steps in data generation and transfer. You should also have a close look at the user and access management and the segregation of duties. Furthermore, the following areas should be checked:

• Audit trail function
• Completeness of print-outs
• Backup management

That is certainly a lot of work which can not be covered in a short internal audit. So it might be advisable to develop a questionnaire or checklist based on a data flow model or Mind Maps. Arrange interviews with system and process owners and maybe get support by an expert from your IT department.

After the audit, report the results and evaluate any (GMP) risk to define necessary actions. And don’t be afraid, negative feedback must be possible. Data Integrity assessments should then be part of every internal audit.

◆  Brexit: the British comment (30-Aug-17 ECA)

After the European Medicines Agency EMA in particular spoke out on the possible future of the trade with medicinal products on a European Union (EU) level, the British now provide some input.

The proclamations of the EMA so far have in parts sounded harsh and resolute: “The UK will become a third country” or “APIs manufactured in the UK will need Written Confirmation” are powerful words.

Now, the United Kingdom’s (UK) government has published a position paper on the possible future trade of goods between the UK and the EU (“Continuity in the availability of goods for the EU and the UK”). This paper sounds different from statements on European level so far. For example, the British government is looking for a free movement of goods and services, including – amongst other things – the continuous recognition of marketing authorisations, registrations and certifications of goods (including medicinal products). Also, inspections (of companies) should be recognised after the withdrawal and double structures for authorities and companies should be avoided. Here, the Qualified Person (QP) is mentioned explicitly. The United Kingdom aims to “avoid the unnecessary disruptive transfer of activities between the EU and the United Kingdom”, especially if such activities have to be duplicated for both markets.

Also the exchange between authorities, including matters in regards to medicinal products, should be maintained and promoted. A welcome proposal, since this is also a matter of consumer safety.

The involved parties have made their positions clear now. The solution will probably lie somewhere in the middle; the suspense continues.

◆  Test for Subvisible Particles: ICH Harmonisation Completed (06-Sep-17 ECA)

With Step 5, harmonisation regarding the use of pharmacopoeial methods for test for subvisible particles in the ICH regions has been completed.

The ICH strives to harmonise GMP and pharmacopeial requirements in its major regions of the EU, the U.S. and Japan. Based on the evaluation by the Q4B Expert Working Group (EWG), the ICH Steering Committee has recommended that the official pharmacopoeial texts, Ph.Eur. 20919, JP 6.07 and USP <788> for the test for subvisible particles can be regarded as comparable, provided that instrument calibration and their SST follow regional GMP requirements. This is not valid for the test of 100-milliliter (mL) parenteral products, because the acceptance criteria of the Japanese Pharmacopoeia are stricter than those of the two others. As always with ICH harmonisation processes, there is an addition stating that the FDA may request a demonstration that the chosen method is acceptable and suitable for a specific material or product, irrespective of its origin. For the EU, the harmonisation signifies among others that an application for approval may contain references to the Japanese Pharmacopoeia e.g. and that this will not lead to difficulties in the approval procedure. Variation applications for method changes (within the cited texts) should also be possible without problems.