July 2022
· 11 min read
The U.S. FDA has issued a revised version of their guidance on “Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production,” which was originally issued in 2006. Most of the changes in the revised version are fairly minor, such as the changing throughout the document of the term “quality control unit” (QCU) to be just “quality unit” (QU).
The most substantive change is to the section “Concluding the Investigation” at the end of the guidance, where Part B. Cautions has been significantly expanded and divided into three new subparts, as follows:
On May 31, 2022, the MHRA launched a consultation on “The future strategy for batch testing of medicinal products in Great Britain.” This consultation closes at 11:45 p.m. on July 26, 2022.
Much of the document consists of the background to the consultation, which, of course, is the UK leaving the EU. This section makes it clear that while the UK wished to have a mutual recognition agreement (MRA) with the EU, this was refused by the EU, and “an MRA with the EU is not a policy approach being considered as part of this consultation.” As Northern Ireland remains within the EU system for medicines, the consultation is only for Great Britain (GB).
The consultation consists of four policy options, as follows:
Again, this removes the role of the RPi and requires a limited number of tests on medicines imported from listed countries. The tests required would depend on the product, such as identity and assay tests for a small molecule or requiring an impurity test for short-shelf-life products. This would be set out in the MA.
Importers would need to hold a manufacturing/import authorization (MIA) and a GMP certificate from the MHRA. The UK QP would be responsible for ensuring that the finished medicinal product batch has undergone the required tests in the UK and could then certify/release the batch for sale on the UK market.
A response to the consultation will be published in due course following its closure on July 26. It will form the conclusion of the review and trigger the two-year notice period after which the policy will be implemented.
All regulatory agencies around the globe are concerned by shortages of medicines and are enacting new legislation and guidance covering this concern. In the EU, Regulation 2022/123 is starting to be implemented, and in the U.S. in 2020, Congress passed the Coronavirus Aid, Relief and Economic Security (CARES) Act to require manufacturers of critical drugs to develop, maintain and implement, as appropriate, risk management plans that identify and evaluate risks to a drug’s supply. As part of the implementation of the CARES Act, the FDA published draft guidance in May 2022 titled “Risk Management Plans to Mitigate the Potential for Drug Shortages.”
This draft guidance requires all “stakeholders” in the supply chain of the drug products to produce risk management plans. The stakeholders are divided into primary, secondary and others. These include the drug product manufacturer, API suppliers, excipient suppliers, and contract laboratories or contract packers.
The draft describes drug products for which risk management plans (RMPs) are required and a separate list of products for which they are recommended. The prescription products requiring RMPs are those that are:
RMPs are recommended for the following products:
The guidance on producing RMPs essentially follows the ICH Q9 quality risk management process, with sections on:
The UK MHRA introduced a new route for the supply of medicines to Northern Ireland (NI) from Great Britain (GB) beginning on January 2022 called the Northern Ireland MHRA Authorisation Route (NIMAR). NIMAR provides a route for the lawful supply of prescription-only medicines (POMs) in compliance with UK and EU rules, when there is a risk that clinical need in NI for that product cannot be met. This includes the supply of medicines that are unlicensed in NI but which are licensed and approved in GB.
The May 2022 guidance provides the following information:
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