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The State of Pharma Quality, GMP Certificates, November Pharma News Update
NSF’s November 2021 pharmaceutical industry update looks at recent changes in guidelines and legislation that will impact the pharmaceutical sector.
This edition includes:
- The U.S. FDA “Report on the State of Pharmaceutical Quality: Fiscal Year 2020” — Key Findings
- U.K.-U.S. GMP Mutual Recognition Agreement Extended
- Draft FDA Guidance: “Microbiological Quality Considerations in Non-Sterile Drug Manufacturing”
- Extension of GMP and GDP Certificates and Time-Linked Authorizations
- EudraGMDP Database Changes
Detailed legislation updates are also available on the NSF Pharma App.
The U.S. FDA “Report on the State of Pharmaceutical Quality: Fiscal Year 2020” — Key Findings
The U.S. FDA recently published its annual “State of Pharmaceutical Quality” report for fiscal year 2020. This report assesses multiple indicators to better understand the pharmaceutical industry’s ability to deliver medicinal products to patients and consumers in the United States. Prepared by the Center for Drug Evaluation and Research (CDER), it presents information on drugs in the pharmaceutical supply chain.
The 2020 report covers the activities of 4,221 drug-manufacturing sites featured in the CDER catalog. Thirty-eight percent of these sites are listed as “no application,” meaning they are manufacturing products marketed without an approved application. These include over-the-counter, unapproved and homeopathic products.
The remaining 2,611 sites (62%) are involved in the manufacture of at least one application product:
- Biological products covered by Biologics License Applications (BLAs)
- Innovator products approved under New Drug Applications (NDAs)
- Generic products approved under the Abbreviated New Drug Application (ANDA) process
Monitoring and Application Approvals During a Global Health Emergency
The COVID-19 pandemic impacted the FDA’s ability to conduct site monitoring and approve new applications during fiscal year 2020. Nevertheless, the organization utilized Mutual Recognition Agreements (MRAs) with the European Union and the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA) to circumvent travel restrictions brought about by the pandemic.
The FDA was also able to request records and information in place of inspections by employing MRAs with other countries. The FDA still carried out 562 drug quality assurance inspections in fiscal year 2020 despite the restrictions. In addition, the agency was able to assess a further 183 sites by using MRA inspection reports. The number of inspections was significantly lower than in the previous fiscal year, when the agency conducted 1,258, with an additional 109 sites assessed using MRAs.
Warning Letters and Import Alerts
While the number of inspections decreased greatly, the number of Warning Letters issued was only slightly lower than in the previous year. Interestingly, it was four times higher in fiscal year 2020 than in 2015. Most Warning Letters were issued to no-application sites and sites manufacturing non-sterile products.
Hand sanitizer products accounted for a major increase in the number of import alerts issued in 2020, which doubled to 128 from the previous year. An unprecedented number of hand sanitizers from Mexico failed to meet requisite standards.
Eventually, the FDA placed all hand sanitizer products from Mexico on a countrywide import alert.
Sanitizers containing methanol were the most recalled products in the past year. These also accounted for a fourfold increase in drug product quality concerns. NSF’s Maxine Fritz and Orsi Dézsi examined the issue in the May 2020 webinar “Make Hand Sanitizer, Not Mistakes: Understand the FDA Policy.”
Since the pandemic continues to disrupt travel arrangements and impact the ability to carry out in-person inspections, the CDER is considering new methods to help ensure product quality and safety. The New Inspection Protocol Project (NIPP) aims to use standardized electronic inspection protocols to collect data in a structured manner. These protocols include questions related to the quality culture observed in facilities.
As the NIPP progresses, it is anticipated that the insights gathered will inform future inspections, assist in the development of policy and influence application-related decision-making.
U.K.-U.S. GMP Mutual Recognition Agreement Extended
On September 27, 2021, it was announced that the U.K. Veterinary Medicines Directorate (VMD) and the U.S. FDA had agreed to extend the scope of the U.K.-U.S. Good Manufacturing Practice (GMP) MRA to include inspections of veterinary pharmaceuticals.
This means that the scope of the U.K.-U.S. MRA is now wider than that of the U.S.-EU MRA, which has not yet been extended to include veterinary medicines.
Draft FDA Guidance: “Microbiological Quality Considerations in Non-Sterile Drug Manufacturing”
The U.S. FDA has issued draft guidance for the industry on “Microbiological Quality Considerations in Non-Sterile Drug Manufacturing.” Comments on this draft should be submitted by November 29, 2021.
The new draft guidance focuses on GMP for controlling objectionable microorganisms and bioburden in non-sterile drugs (NSDs), including solid, semisolid and liquid dosage forms. It discusses product development considerations, risk assessments and certain GMPs that are particularly relevant to microbiological control in a manufacturing operation for an NSD. It also provides recommendations to help manufacturers assess the risk of contamination of their NSDs with objectionable microorganisms and establish appropriate specifications and manufacturing controls to prevent such contaminations.
The draft guidance states that the FDA “does not expect application holders of approved drug products to amend the product specification in cases where it is inconsistent with the recommendations discussed in this guidance.”
However, if a manufacturing change that may affect the risk of microbiological growth is proposed, “FDA assessors may request that the application holders update the microbiological testing information in the product specification during assessment and before approval,” and “application holders may wish to consider updating a given drug product specification as recommended in this guidance.”
Extension of GMP and GDP Certificates and Time-Linked Authorizations
On September 30, 2021, the European Medicines Agency (EMA) announced that it had updated its “Guidance for medicine developers and other stakeholders on COVID-19” to the effect that the European medicines regulatory network had extended until the end of 2022 the validity of Good Manufacturing Practice (GMP) and Good Distribution Practice (GDP) certificates and time-limited manufacturing, import and wholesale authorizations.
GMDP Database Changes
The EMA has announced a significant change that will impact all manufacturers, importers and distributors of both human and veterinary medicines into the EU and European Economic Area (EEA) whose information is recorded in the EudraGMDP database.
The new regulatory framework for veterinary medicines (Regulations 2019/6 and 2021/16, Article 9(h)) requires changes to the EudraGMDP database that will come into effect on January 28, 2022. The main change will be the integration of EudraGMDP with the EMA’s Organisation Management Service (OMS). This is an important development for manufacturers, importers and distributors to be aware of, to ensure that their sites are registered in the OMS.
As of January 28, 2022, before applying for a new or updated manufacturing or wholesale distribution authorization with national competent authorities, please check whether your organization is correctly registered in the OMS.
What Is the OMS?
The EMA first launched the OMS in 2016 to support regulatory activities throughout the EU. The OMS provides a single source of validated organizational information that can be used as a reference for regulatory procedures and business processes. It stores master data including the names and locations of a range of organizations, such as marketing authorization holders, sponsors, regulatory authorities and manufacturers.
When it launched, the EMA said that use of the OMS would become mandatory over time, and the new integration with the EudraGMDP database will make it mandatory for many organizations.