FDA Guidance, New Regulatory Collaboration Pilots and More

The International Coalition of Medicines Regulatory Authorities (ICMRA) has announced the initiation of two regulatory collaboration pilots addressing facility inspections and chemistry, manufacturing and controls (CMC) as well as post-approval change (PAC) submission assessments and related regulatory actions. The pilots are being operationalized under the auspices of ICMRA to explore the feasibility and potential for further collaboration and convergence among regulators in specific data expectations and assessment approaches when assessing manufacturing facilities for pre-approval and pre-license applications (PAIs and PLIs) and reviewing PACs and PAC management protocols.

The two pilots, one focused on collaborative assessments of CMC submissions and the other on hybrid inspections, are to inform pre-market or PAC CMC assessment of drug applicants. Each of the pilots will involve two or more national regulatory authorities collaborating in the effort. Please note that the actual post-approval change submission should follow the normal regulations and procedures in each participating region.

Each pilot aims to conduct three assessments or collaborative hybrid inspections over an anticipated duration of 1-1.5 years and then issue learnings and recommendations on how to operationalize these programs in the future to benefit the industry and regulators. More information related to the vision, goals and specific considerations for each of the pilots is provided in the Supplementary Information section of the announcement.

Industry sponsors are invited to apply to participate in one or both collaboration pilots.

Who Can Apply?

Sponsors planning to file an application for a new product or for post-approval changes of approved products to more than one regulatory agency. The proposal should focus on therapeutics (including both small-molecule and biological products), which can include products intended for the treatment of patients with COVID-19; breakthrough, PRIME, Sakigake, etc., products; or products deemed medically necessary/critical medicine. The submission should be intended to be submitted to multiple regulatory authorities at the same time and should be provided to all participating regulatory authorities.

Sponsors intending to submit a proposal for the inspection pilot should confer with the management of the facility and ensure that the facility will be inspection ready and can host a collaborative hybrid inspection. The facility should satisfy itself that it has appropriate IT infrastructure and availability of necessary interpretation services and can coordinate with at least two inspectorates across different time zones. Please refer to the application form for further detail on necessary requirements.

What To Submit?

Complete the appropriate pilot application form available on the ICMRA website (see links).

• Application Form for Collaborative Assessment
• Application Form for Collaborative Hybrid Inspection

The application should be sent to each email address using EudraLink. EudraLink is a secure file transfer application provided by EMA, allowing drug companies and national medicine authorities to be able to exchange highly sensitive documentation with the highest level of security.

When To Apply?

Interested sponsors can send completed application forms beginning June 15, 2022. The ICMRA collaboration pilots plan to conduct a rolling review of submitted applications, with the aim of starting the first pilot in an early September 2022 time frame.

The U.S. FDA is announcing the availability of a draft guidance titled “Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross-Contamination.” This guidance revises the final guidance of the same title issued on April 17, 2013, and expands the scope of the guidance to include all compounds containing a beta-lactam ring in their structure. All beta-lactam compounds, including non-penicillin beta-lactam antibacterial drugs as well as non-antibacterial beta-lactam compounds (including intermediates and derivatives), have the potential to cause allergic reactions and represent a life-threatening risk to certain patients.

This draft guidance describes methods, facility design elements and controls that are important in preventing drugs from being cross-contaminated with non-penicillin beta-lactam antibacterial drugs or non-antibacterial beta-lactam compounds and makes recommendations for how manufacturers can be compliant with current good manufacturing practice requirements for preventing cross-contamination. The guidance also provides information regarding the relative health risk of, and the potential for, allergic reactions due to cross-reactivity in the classes of non-penicillin beta-lactam antibacterial drugs and non-antibacterial beta-lactam compounds.

This guidance recommends that manufacturers have complete and comprehensive separation between non-penicillin beta-lactam antibacterial drugs and the manufacturing operations of other drugs. For manufacturers of non-antibacterial beta-lactam compounds, the guidance provides recommendations on cross-contamination prevention strategies, including examples of relevant design features and control approaches for those seeking to justify a cross-contamination prevention strategy other than complete and comprehensive separation, when appropriate.

Significant changes from the 2013 guidance include:

• Clarifying that the scope of the guidance also includes all compounds, including intermediates or derivatives, which are not a penicillin, have a chemical structure that includes one or more beta-lactam rings, and have a mechanism of action other than an antibacterial mechanism of action
• Providing the FDA’s interpretation of terms used in this guidance, such as “allergic reaction,” “cross-reactivity,” and “complete and comprehensive separation”
• Clarifying the distinction between non-penicillin beta-lactam antibacterial drugs and non-antibacterial beta-lactam compounds — in terms of the cross-contamination and patient exposure risks and the control strategies appropriate for manufacturing operations involving each category
• Providing recommendations for drug manufacturers that seek to justify alternative cross-contamination prevention strategies for non-antibacterial beta-lactam compounds

How do you design a risk-based and cost-effective validation program to meet cGMP expectations? This webinar, presented by Pete Gough, provides an overview of the new science and the risk-based approach to validation that is now enshrined in guidance from both the U.S. FDA and the EU.

The U.S. FDA has published a new Manual of Policies and Procedures (MAPP), “Assessment of the User Interface of a Drug-Device Combination Product Submitted in a Pre-ANDA Communication or an ANDA” (5223.6). This MAPP describes the Office of Generic Drugs’ (OGD) and the Office of Surveillance and Epidemiology’s (OSE) policies and procedures for the assessment of the user interface of a drug-device combination product (generic combination product) submitted in an abbreviated new drug application (ANDA) or a pre-ANDA communication.

FDA’s draft guidance for the industry, “Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA,” provides a systematic approach for ANDA applicants to use in identifying and analyzing differences between the user interface of a proposed generic combination product and the user interface of its reference listed drug. Applicants should consult that guidance for recommendations on how to perform comparative analyses and what information to submit to the FDA in their ANDAs.

Both OGD and OSE have differing expertise that may inform the review of comparative analyses of generic combination products. This MAPP clarifies OGD’s and OSE’s roles and responsibilities for the assessment of comparative analyses and comparative use human factors studies and explains when OGD will consult OSE. Additionally, it outlines OGD’s and OSE’s policy for regularly scheduled meetings between OGD and OSE to support shared learning, awareness and consistency — where applicable — in the assessment and characterization of user interface differences for combination products submitted under different application pathways (e.g., 505(j), 505(b)(2) and 351(k)).

For additional details, please refer to the full text of the MAPP.

NSF’s pharma and biotech consulting and training team will be attending the Making Pharmaceuticals Exhibition and Conference in Ireland on September 27 and 28.

Marie O’Callaghan and Brian Cleary will be at stand 320 at the RDS in Ballsbridge, meeting clients and attendees over the course of the event.

This is the first-ever Making Pharmaceuticals event in Ireland. You can book tickets to attend here.