27/28 October 2021
Before the COVID-19 pandemic, almost all audits and inspections conducted took place on site. From time to time, auditors used questionnaires and checklists. But these were or are more or less a supplement in the overall supplier qualification process.
When the GMP guidance was written and introduced, no one had thought of a pandemic or anything like that. Some of the requirements to conduct on-site audits are therefore clear, for example in Article 46(f) EU Directive 2001/83/EC:
"the holder of the manufacturing authorisation shall verify compliance by the manufacturer and distributors of active substances with good manufacturing practice and good distribution practices by conducting audits at the manufacturing and distribution sites..."
Distant assessments, as we understand it recently, e.g. with direct video and audio communication, have not been addressed or even regulated so far. Last year, for the given occasion, a question and answer document was prepared in the EU, which at least addresses distant assessments contucted by the authorities.
Question and answer 2.2 deals with GMP certificates and manufacturing/import authorisations. Due to the current difficulties in carrying out GMP on-site inspections, it is often not possible for authorities to extend the validity of GMP certificates accordingly. This should now be possible in order to avoid difficulties in the availability of medicinal products - until the end of 2021. The validity of manufacturing/import licences should also be extended (if they are time-limited).
Also for new sites, a distant assessment by a competent EU/EEA authority may be an option. A GMP certificate can then be issued depending on the outcome of the assessment. However, it should be stated that the certificate was issued on the basis of a distant assessment. In addition, an on-site inspection should be carried out as soon as circumstances permit. Limited or short on-site inspections in the EEA should also be considered at this time if compatible with travel restrictions, health measures and other constraints.
Due to the pandemic, almost all inspectorates have postponed routine inspections. Alternative approaches, including distant assessments, were also increasingly used. A uniform procedure was not discernible for some time. Then, in November, EMA published a GMP/GDP guidance document (EMA/335293/2020) for such distant assessments, which is intended to provide guidance for inspectors. In addition to a detailed definition, prerequisites and the most important points in preparation and implementation are also described. However, the authors clearly point out that distant assessments are not intended as a substitute for on-site inspections outside crisis situations and that on-site inspections should be carried out as soon as circumstances allow again.
And how does the industry see distant assessments?
The companies themselves currently have little choice but to resort to these options as well. It is advisable that each company carries out an individual risk assessment and precisely documents the result achieved. This should also include plans on what to do when restrictions are lifted to ensure that on-site audits are resumed and repeated in a timely manner.
Where own on-site audits are not currently possible, the QP may refer distant assessments and also take into account the results of inspections by competent authorities. Decisions should be based on a scientific basis and an adequate and documented risk assessment.
A distant assessment is therefore a possible (and currently reasonable) way to assess a supplier's or CMO's GMP compliance when an on-site audit is not possible. This also applies for the future. Within the framework of a risk-based supplier qualification, distant assessments will certainly be increasingly carried out, but they cannot and must not replace on-site audits.