One of the tasks required by GMP regulations, which is also a part of business continuity for Marketing Authorisation Holders and so-called contract givers, is to qualify suppliers and contract acceptors. One important part of such a qualification process is the performance of an on-site audit. Because of the Corona crisis, the fact that an auditor has to visit a site currently presents a potential risk to all persons involved or might simply not be possible because of travel bans.
If an onsite audit is currently not possible, a risk-based supplier qualification process can be supported by a remote or virtual audit. Such an audit may be conducted through various communication channels such as video calls or other appropriate tools available. In fact, an auditor could be sitting in the office or even at home conducting the audit.
The ICH Guideline Q9 lists a number of points that should be considered during audit planning. Those are also helpful during final and ongoing assessment and qualification.
Most of the benefits associated with on-site audits are tours of manufacturing facilities, warehouses, and laboratories. However, a lot of time is spent with talking to personal, listening to explanations and document reviews. This could also be done in a remote audit.
What are the regulators saying?
When the rules and regulations were written and implemented, nobody had thought about such a situation as a pandemic. Some of the rules are quite clear about auditing, for example:
Article 8 of EU-Directive 2001/83/EC
The application of a marketing authorization shall be accompanied by a “written confirmation that the manufacturer of the medicinal product has verified compliance of the manufacturer of the active substance with principles and guidelines of good manufacturing practice by conducting audits.”
EU-GMP Guidelines Annex 16 (Certification by a Qualified Person and Batch Release):
1.7.3 “All audits of sites involved in the manufacture and the testing of the medicinal products and in the manufacture of the active substance have been carried out and that the audit reports are available to the QP performing the certification.”
2.2 vi “Repeated audits should be performed in accordance with the principles of Quality Risk Management.”
Now MHRA has published their thoughts in a blog on “MHRA Good Practice (GxP) inspections during the COVID19 outbreak“. MHRA itself will “focus on service continuity by using alternative approaches for routine regulatory oversight, such as office-based assessment and the sharing of information within the international regulatory network“, as they stated in their article from 20 March “New arrangements for MHRA Good Practice (GxP) inspections due to coronavirus (COVID-19)”.
In the blog, MHRA give further details about what remote assessments could look like:
- organisations are asked to provide electronic copies of documents and other information for review off-site;
- teleconferences and e-mail will be used to follow up;
- necessary on-site portions of routine surveillance such as plant tours will be re-scheduled for when travel restrictions are lifted;
- make use of available GxP information from MRA partners and other collaborating regulators.
MHRA does not directly allow remote audits for companies but acknowledges the fact that “organisations working in the manufacturing and supply of medicines may also need to adapt their procedures to maintain supply chain vigilance and supplier oversight as audits become difficult to schedule“.
Even before the crisis with the associated travel bans, PIC/S has started to develop a Guidance document on GMP Inspection Reliance to help Competent Authorities (CA) prioritising resources for GMP inspections. The document introduces a process for desk-top assessments of GMP compliance of facilities in other countries. It is a non-binding high-level guidance for ICMRA and PIC/S participating authorities, but the process can also serve as a model for the pharmaceutical industry for their risk-based supplier qualification and current auditing activities.
It is recommended that every company documents the risk assessment undertaken and the outcome achieved by using a remote audit approach. This should also include what plans will be put in place when the current restrictions are removed to ensure a resumption of on-site audits in a timely manner.