Measures to reduce industry burden for stronger GMP

Government and industry prepare measures to reduce the burden brought by stronger GMP enforced on aseptic drugs

KPBMA researches standards for large-volume IV solutions with HK Inno.N, JW Pharmaceutical, Dai Han Pharm

MFDS plans to establish guidelines for contamination control strategies, PUPSIT, etc.

With the Ministry of Food and Drug Safety set to enforce the revised GMP standards for aseptic drugs reflecting the international Pharmaceutical Inspection Co-operation Scheme (PIC/S) standards from December, measures are being prepared by the industry to reduce its burden.

 

Ahead of its rejoin into PIC/S in 2023, the MFDS announced the “Regulations on Drug Manufacturing and Quality Control (MFDS Notice)” which outlines a risk-based, systematic contamination control strategy to enhance the quality assurance of aseptic pharmaceuticals.

 

At the time, in consideration of the need for sufficient preparation time for all pharmaceutical companies to establish contamination management strategies, the government decided to implement the regulations first for aseptic finished pharmaceutical products until 2 years after the announcement, and then for aseptic active pharmaceutical ingredients until 3 years after the announcement.

 

The implementation of measures such as PUPSIT (Pre-Use Post-Sterilization Integrity Testing) for verifying the integrity of sterilizing filters has been granted a uniform grace period—up to three years from the date of the revised GMP regulation—considering the need for additional preparation time for revalidation of aseptic processes and administrative procedures for GMP compliance determinations under the current guidelines.

 

However, as the implementation of certain requirements for sterile finished pharmaceutical products approaches, including ▲the obligation to establish and implement a systematic contamination control strategy for the manufacture of aseptic drugs, ▲ the establishment of individual manufacturing and quality control standards (GMP) for advanced biopharmaceuticals, and ▲ the clarification of detailed specifications for the types of formulations subject to GMP compliance assessment, as well as the procedures and methods for such assessments, some pharmaceutical companies are halting or withdrawing their aseptic product manufacturing operations on itself.

 

Particularly, following the announcement by Ildong Pharmaceutical that it would discontinue production and supply of its ‘Ativan Inj,’ which has experienced repeated supply instability over the past 3 years since 2022, speculation has emerged that the ripple effects of the strengthened GMP standards for aseptic drugs may have begun.

 

Jung-yeon Kim, director of the MFDS

In response, Jung-yeon Kim, director of the MFDS's Pharmaceutical Quality Division, said at a briefing with reporters on the 10th, “There have been ongoing issues with the supply of Ativan, and we have been in constant communication with the manufacturer since the end of last year.

 

The company did not decide to withdraw from the market due to the stricter GMP standards, rather, there were internal circumstances, such as product profitability and drug price issues.” It is known that a similar sentiment was conveyed at a meeting between the MFDS and the heads of aseptic drug manufacturers on April 30.

 

Kim explained, “About 20 companies participated in a factory manager meeting last month.

 

At the time, the MFDS conveyed its position that it had no choice but to apply the same standards used by the 52 PIC/S member countries.

 

Manufacturers also expressed difficulties in the preparation process, and that the MFDS should prepare supporting data through a research platform to reduce the burden on the industry and provide technical and regulatory support.” Instead of implementing the PIC/S-level GMP strengthening measures for aseptic preparations as scheduled in December, the MFDS plans to establish guidelines for large-volume IV solutions, contamination control strategies (CCS), and PUPSIT, referring to the results of the “Study on the Harmonizing the GMP Regulations on Aseptic Drugs” currently being conducted by the Korea Pharmaceutical and Bio-Pharma Manufacturers Association (KPBMA) Kim added, “In the case of large-volume IV solutions, strengthening GMP standards to comply with EU Annex 1 would require establishing a contamination control strategy for each batch, which companies find most burdensome.

 

We are conducting research with three companies— HK Inno.N, JW Pharmaceutical, and Dai Han Pharm— and KPBMA to establish grounds that show there will be no changes in GMP quality even with eased standards.” The three companies participating in this study account for 90% of the large-volume IV solution market, and since November last year, they have been meeting with the KPBMA and MFDS to develop a research protocol and have completed kick-off meetings and preliminary workshops.

 

Cheon-Woon Cheon, a research committee member at the KPBMA

Cheon-Woon Cheon, a research committee member at KPBMA who is leading the study, said, “We have held meetings with the MFDS and companies to clearly set the direction of the project, and our goal is to produce results by October so that they can be reflected in the policy.” Cheon added, “The revision of Annex 1 has placed a significant burden on manufacturers of sterile products.

 

We are seeking ways to reduce this burden and are currently researching the appropriate level of validation required for processes such as formulation, filtration, filling, and sterilization.” In this regard, Kim said, “There is no single correct answer in GMP.

 

What matters is having a technically and scientifically justified rationale that achieves the intended goal.

 

I hope that the research findings will provide a sufficient basis to support the level of aseptic control expected by PIC/S.” Through this study, the MFDS expects not only to relax the standards for large-volume IV solutions but also to establish guidelines for CCS and PUPSIT.

 

Cheon said, “Small companies lack experience and have difficulty just approaching CCS.

 

Our goal is to establish guidelines by the end of the year that small companies can follow by conducting research through large companies.” In the case of PUPSIT, which is scheduled to be implemented in December next year, a separate project team has been formed to establish its guidelines.

 

Kim said, “In principle, each company is responsible for implementing GMP issues per the system, but the MFDS has tried to provide assistance through industry communication.

 

Since November last year, we have been meeting with associations and industry representatives to ask them to follow the international standards, and we have formed a consensus on common research tasks.” Kim added, “While direct financial support is difficult at this time, we are exploring ways to reduce industry burdens through regulatory or technical support.

 

Once research results are available, we aim to establish GMP management measures with a clear direction, which should also lead to cost savings.”