FDA’s Mutual Reliance Initiative – Saving FDA Some Money at the Expense of Inspectional Quality?

By Mark I. Schwartz –

The Mutual Reliance Initiative was announced by FDA a couple of years back.  It has as its goal “…to increase…[FDA’s]…exchange, with the European Commission and the European Medicines Agency, of information that is critical to making decisions that protect our public health.” 

What this cryptic statement is actually describing is FDA’s interest in exploring the possibility of relying on Europe’s inspections of EU drug facilities so that the agency will not have to inspect these facilities themselves, in the hope of economizing a significant fraction of its inspection budget.  According to Howard Sklamberg, FDA’s Deputy Commissioner for Global Regulatory Operations and Policy, “…we cannot be the inspectors for the world.  Hence, we need to effectively direct our resources in a risk-based manner as we grapple with this tremendous volume of imported goods.”

The Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA) allows FDA to enter into arrangements with foreign governments to recognize the inspection of foreign establishments that are registered under the FDCA “…in order to facilitate risk-based inspections…”

FDASIA section 712 (FDCA section 809):

(a) INSPECTION.—The Secretary—

(1) may enter into arrangements and agreements with a foreign government or an agency of a foreign government to recognize the inspection of foreign establishments registered under section 510(i) in order to facilitate risk-based inspections in accordance with the schedule established in section 510(h)(3);

(2) may enter into arrangements and agreements with a foreign government or an agency of a foreign government under this section only with a foreign government or an agency of a foreign government that the Secretary has determined as having the capability of conduction inspections that meet the applicable requirements of this Act; and

(3) shall perform such reviews and audits of drug safety programs, systems, and standards of a foreign government or agency for the foreign government as the Secretary deems necessary to determine that the foreign government or agency of the foreign government is capable of conducting inspections that meet the applicable requirements of this Act.

(b) RESULTS OF INSPECTION.—The results of inspections performed by a foreign government or an agency of a foreign government under this section may be used as—

(1) evidence of compliance with section 501(a)(2)(B) or section 801(r); and

(2) for any other purposes as determined appropriate by the Secretary.

[Emphasis added.]

For well over a decade now (in other words, this predates the explicit grant of authority under FDASIA) the EU and FDA have been interested in reaching an agreement on cGMP inspections that would allow the regulatory bodies to avoid duplication of their surveillance activities and lower the overall costs of their respective programs.  And the savings would not be negligible, as close to half of FDA’s drug inspections (43% to be precise) are performed in EU countries, according to Dara Corrigan, FDA’s Associate Commissioner for Global Regulatory Policy.  It should be noted that Ms. Corrigan provided this estimate prior to the United Kingdom’s Brexit vote, which will carve out a number of UK drug facilities from EU oversight over the coming years.

In a recent interview, Ms. Corrigan said that $18.5 million in inspection costs could be used elsewhere if FDA did not inspect facilities in the EU.  And these costs are only going to increase as the number of domestic inspections over the past several years has gone down while the number of foreign inspections has increased commensurately.  That trend is expected to continue.

Historically, one of the main stumbling blocks has been the disparate regulatory structures between the U.S. and the EU, as the EU has 28 member states and most, if not all, of these states have their own medicines authorities, in addition to the European Medicines Agency (EMA), which is the EU agency responsible for the protection of public health through the scientific evaluation and supervision of medicines.  This web of overlapping state and super-state drug authorities has made it difficult for FDA to reach agreement with the EU.

Another stumbling block has been the sharing of trade secret information between FDA and the EMA. The EMA has been sending unredacted summaries of EU inspections to FDA for some time, however, the FDA’s reports to the EMA have been redacted, as by law it is only allowed to share trade secret information with a foreign government if the FDA Commissioner certifies that the foreign government has the ability to protect the information from disclosure (Section 708 FDASIA).

The EMA already has bilateral mutual reliance agreements with other regulatory authorities but, for years, has been most interested in securing one with the U.S., its most important trading partner.

Ms. Corrigan has stated that the agency expects to make a decision this year as to whether an EU member state is capable of performing drug facility inspections to FDA’s satisfaction, and whether the agency can confidently rely on those findings.

However, the notion of having a foreign inspectorate perform drug inspections on FDA’s behalf, when the inspections performed by FDA’s own investigators are already so inconsistent, is problematic at best.  Indeed, FDA representatives have long acknowledged that the agency doesn’t have an objective method for measuring quality in the drug industry (for instance, at which facilities are cGMPs improving?  By how much and in what way?)  Nor do they have a reliable method for making cGMP comparisons between facilities manufacturing similar products, or for comparing the results from within a facility over multiple inspections.[1]

It would seem that rectifying these significant lacunae in FDA’s inspectional responsibilities should be the first order of business for the agency, prior to even considering delegating the responsibility for EU inspections to a foreign inspectorate which is not schooled in FDA’s precise cGMP requirements.

We will continue to keep you posted on all developments in this regard.

[1]  This author will acknowledge that, last year, the agency published a draft guidance on Quality Metrics, which has yet to be finalized, and it is also developing a New Inspection Protocol Project, both of which seek to remedy these weaknesses in the agency’s inspection process.  However, these projects are in their earliest stages, they remain largely untested, and it is unclear at this point whether they will lead to more consistency in inspectional results.