BY Mark Birse, Vice President, Technical, Parexel Regulatory & Access
Increasingly over the last 10 years global regulators have looked to see how a greater reliance on desk-based inspection activities can support their surveillance programs. This approach can be seen throughout the product lifecycle with elements of inspections being conducted remotely for GCP, GPvP, GMP and GDP.
Regulators have also had a focus on how greater reliance can be placed on each other’s outcomes, given that with the complexity of global supply chains, the demand for inspecting pharmaceutical facilities far exceeds what any one agency can accomplish.
This is achieved either through formal relationships such as Mutual Recognition Agreements or more informal reliance mechanisms.
Some examples globally of these approaches can be seen with:
- FDA, US: FDASIA Sec. 706 which allows FDA to obtain certain records and other information from a drug manufacturer in lieu of or in advance of an inspection (1)
- MHRA, UK: Office Based Evaluation and Risk Assessment program for GDP (OBERA) (2) and Office Based Inspection (OBI) for elements of GCP inspections (3)
- TGA, Australia: GMP clearance for an overseas manufacturing site (4)
- EMA: Mutual recognition agreements (MRAs) (5)
- PIC/S: GMP Inspection Reliance (6)
A combination of onsite audits and desk-based reviews has also been adopted by pharmaceutical companies when assessing suppliers and contract manufacturers for several years as part of their supplier management programs. Subsequently, this approach is assessed during regulatory inspections to confirm if an appropriate level of oversight is being maintained.
When used appropriately and in a risk proportionate way, desk-based inspections can bring a high level of confidence around on-going operations. Acknowledging that this approach is more likely to be used when there has been a previous on-site inspection undertaken in the past.
Limited reporting and remote assessment of metrics and compliance by companies to regulators can also be used to reassess any risk-based inspection intervals, such as the MHRA interim reporting form. (7)
All this said, there are clear limitations with undertaking desk-based inspections. Aspects relating to facilities, instrument/equipment operation and staff behaviors are hard to assess remotely.
Balancing supply and ensuring continuity
One of the hardest dilemmas for regulators is the balance of ensuring the safety of medicines vs availability and avoidance of shortages.
Regulators need to consider what approaches they can take when the supply of product is disrupted, which could make a commonly available product become one at a risk of shortage.
Therefore, knowing that on occasion non-compliant facilities, with additional controls put in place, are required to maintain supply, it seems appropriate that if an inspection cannot be undertaken due to global circumstances, then a desk-based review can fill the gap until it can be performed.
A tool in a time of crisis
Global inspection programs often get disrupted by a variety of reasons, and in the last few years have been affected by:
- Political instability
- Risk of terrorism
- Natural events such as 2010 eruptions of Eyjafjallajökul, Iceland and the subsequent volcanic ash cloud grounding flights
- Insufficient funding, such as during Government shutdown
In 2020, we are seeing the viral pandemic of Covid-19 causing significant disruption. In March, the FDA postponed most foreign inspections scheduled through April, because of federal guidelines prohibiting travel for government workers (i.e., responsibly managing the risk of endangering their health through the conduct of essential duties) and other regulators globally are taking similar approaches.
Indications are that this issue will remain for an extended period and as such alternative approaches will be required. Regulators are going to have to grapple with some difficult scenarios concerning global development and supply of pharmaceuticals and active ingredients, medical devices, and health-related products. Considering how they can support development and approval of potential treatments, vaccines or diagnostics for Covid-19, which may include new production facilities, in a timely yet safe manner.
Equally though, at a time where regulatory inspections are being stepped back due to ongoing issues, regulators also need to be prepared to take a more considered and risk proportionate approach to pharmaceutical company audit programs during this difficult period.
How can Parexel help?
Parexel’s Regulatory & Access consulting organization includes former regulators from global agencies including the U.S. FDA, U.K.’s MHRA and NMPA in China and is exceptionally well placed to help companies facing potential supply problems or regulatory uncertainty.
As supply chains need to be changed manufacturers may be concerned that an inspection will delay a quick approval of a supplement. Our compliance team can help mitigate risks of unnecessary delays by assisting with site selection, assessment of site-readiness, and to strategize about possible inspection waivers.